SUPPORT THE WORK

GetWiki

DNA

ARTICLE SUBJECTS
aesthetics  →
being  →
complexity  →
database  →
enterprise  →
ethics  →
fiction  →
history  →
internet  →
knowledge  →
language  →
licensing  →
linux  →
logic  →
method  →
news  →
perception  →
philosophy  →
policy  →
purpose  →
religion  →
science  →
sociology  →
software  →
truth  →
unix  →
wiki  →
ARTICLE TYPES
essay  →
feed  →
help  →
system  →
wiki  →
ARTICLE ORIGINS
critical  →
discussion  →
forked  →
imported  →
original  →
DNA
[ temporary import ]
please note:
- the content below is remote from Wikipedia
- it has been imported raw for GetWiki
{{about||a non-technical introduction to the topic|Introduction to genetics|other uses}}{{pp-vandalism|small=yes}}{{pp-move-indef}}{{short description|Molecule that encodes the genetic instructions used in the development and functioning of all known organisms and many viruses}}{{Use dmy dates|date=August 2018}}File:DNA Structure+Key+Labelled.pn NoBB.png|thumb|right|upright=1.55|The structure of the DNA double helix. The atoms in the structure are colour-coded by element and the detailed structures of two base pairbase pair File:ADN animation.gif|thumb|The structure of part of a DNA double helixdouble helixDeoxyribonucleic acid ({{IPAc-en|audio=en-us-Deoxyribonucleic_acid.ogg|d|iː|ˈ|ɒ|k|s|ɪ|ˌ|r|aɪ|b|oʊ|nj|uː|ˌ|k|l|iː|ɪ|k|,_|-|ˌ|k|l|eɪ|-}};{{MerriamWebsterDictionary|deoxyribonucleic acid}} DNA) is a molecule composed of two chains that coil around each other to form a double helix carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.The two DNA strands are also known as polynucleotides as they are composed of simpler monomeric units called nucleotides.BOOK, Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P, Molecular Biology of the Cell, 6th, Garland, 2014,weblink Chapter 4: DNA, Chromosomes and Genomes, 978-0-8153-4432-2, no,weblink" title="web.archive.org/web/20140714210549weblink">weblink 14 July 2014, dmy-all, WEB, Purcell, Adam, vanc, DNA,weblink Basic Biology, no,weblink" title="web.archive.org/web/20170105045651weblink">weblink 5 January 2017, Each nucleotide is composed of one of four nitrogen-containing nucleobases (cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, pyrimidines and purines. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine.Both strands of double-stranded DNA store the same biological information. This information is replicated as and when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences. The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation.Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms (animals, plants, fungi and protists) store most of their DNA inside the cell nucleus as nuclear DNA, and some in the mitochondria as mitochondrial DNA or in chloroplasts as chloroplast DNA.BOOK, Russell, Peter, vanc, iGenetics, Benjamin Cummings, New York, 2001, 0-8053-4553-1, In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm, in circular chromosomes. Within eukaryotic chromosomes, chromatin proteins, such as histones, compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.DNA was first isolated by Friedrich Miescher in 1869. Its molecular structure was first identified by Francis Crick and James Watson at the Cavendish Laboratory within the University of Cambridge in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, who was a post-graduate student of Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials.JOURNAL, Mashaghi A, Katan A, A physicist's view of DNA, De Physicus, 24e, 3, 59–61, 2013, 1311.2545v1, 2013arXiv1311.2545M,

Properties

File:DNA chemical structure.svg|thumb|upright=1.35|Chemical structure of DNA; hydrogen bondhydrogen bondDNA is a long polymer made from repeating units called nucleotides.BOOK, Saenger, Wolfram, vanc, Principles of Nucleic Acid Structure, Springer-Verlag, New York, 1984, 0-387-90762-9, BOOK, Alberts, Bruce, Johnson, Alexander, Lewis, Julian, Raff, Martin, Roberts, Keith, Walters, Peter, vanc, Molecular Biology of the Cell, Fourth, Garland Science, 2002, New York and London, 0-8153-3218-1, 145080076,weblink no,weblink 1 November 2016, dmy-all, The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes.JOURNAL, Irobalieva RN, Fogg JM, Catanese DJ, Catanese DJ, Sutthibutpong T, Chen M, Barker AK, Ludtke SJ, Harris SA, Schmid MF, Chiu W, Zechiedrich L, Structural diversity of supercoiled DNA, Nature Communications, 6, 8440, October 2015, 26455586, 4608029, 10.1038/ncomms9440, 2015NatCo...6E8440I, In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, and have the same pitch of 34 angstroms (Ã…) (3.4 nanometres). The pair of chains has a radius of 10 angstroms (1.0 nanometre).JOURNAL, Watson JD, Crick FH, Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid, Nature, 171, 4356, 737–38, April 1953, 13054692, 10.1038/171737a0,weblink PDF, 1953Natur.171..737W, no,weblink" title="web.archive.org/web/20070204110320weblink">weblink 4 February 2007, dmy-all, According to another study, when measured in a different solution, the DNA chain measured 22 to 26 angstroms wide (2.2 to 2.6 nanometres), and one nucleotide unit measured 3.3 Ã… (0.33 nm) long.JOURNAL, Mandelkern M, Elias JG, Eden D, Crothers DM, The dimensions of DNA in solution, Journal of Molecular Biology, 152, 1, 153–61, October 1981, 7338906, 10.1016/0022-2836(81)90099-1, Although each individual nucleotide is very small, a DNA polymer can be very large and contain hundreds of millions, such as in chromosome 1. Chromosome 1 is the largest human chromosome with approximately 220 million base pairs, and would be 85 mm long if straightened.DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together.BOOK, Berg J, Tymoczko J, Stryer L, 2002, Biochemistry, W.H. Freeman and Company, 0-7167-4955-6, These two long strands coil around each other, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside, and a base linked to a sugar and to one or more phosphate groups is called a nucleotide. A biopolymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.JOURNAL, IUPAC-IUB Commission on Biochemical Nomenclature (CBN), Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents. Recommendations 1970, The Biochemical Journal, 120, 3, 449–54, December 1970, 5499957, 1179624, 10.1042/bj1200449,weblinkweblink" title="web.archive.org/web/20070205191106weblink">weblink yes, 2007-02-05, The backbone of the DNA strand is made from alternating phosphate and sugar residues.JOURNAL, Ghosh A, Bansal M, A glossary of DNA structures from A to Z, Acta Crystallographica Section D, 59, Pt 4, 620–26, April 2003, 12657780, 10.1107/S0907444903003251, The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These are known as the 3′-end (three prime end), and 5′-end (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. When imagining DNA, each phosphoryl is normally considered to "belong" to the nucleotide whose 5′ carbon forms a bond therewith. Any DNA strand therefore normally has one end at which there is a phosphoryl attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers directionality (sometimes called polarity) to each DNA strand. In a nucleic acid double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA.File:DNA orbit animated static thumb.png|thumb|upright|A section of DNA. The bases lie horizontally between the two spiraling strandsCreated from PDB 1D65 ((:File:DNA orbit animated.gif|animated version)).]]The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases.JOURNAL, Yakovchuk P, Protozanova E, Frank-Kamenetskii MD, Base-stacking and base-pairing contributions into thermal stability of the DNA double helix, Nucleic Acids Research, 34, 2, 564–74, 2006, 16449200, 1360284, 10.1093/nar/gkj454, In the cytosol of the cell, the conjugated pi bonds of nucleotide bases align perpendicular to the axis of the DNA molecule, minimizing their interaction with the solvation shell. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine, forming A-T and G-C base pairs.BOOK, Burton E., Tropp, vanc, Molecular Biology, 4th, 2012, Jones and Barlett Learning, Sudbury, Mass., 978-0-7637-8663-2, WEB,weblink Watson-Crick Structure of DNA, 1953, Steven, Carr, vanc, Memorial University of Newfoundland, 13 July 2016, no,weblink" title="web.archive.org/web/20160719095721weblink">weblink 19 July 2016, dmy-all,

Nucleobase classification

The nucleobases are classified into two types: the purines, A and G, which are fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T. A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.JOURNAL, Verma S, Eckstein F, Modified oligonucleotides: synthesis and strategy for users, Annual Review of Biochemistry, 67, 99–134, 1998, 9759484, 10.1146/annurev.biochem.67.1.99,

Non-canonical bases

Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. However, in several bacteriophages, such as Bacillus subtilis phages PBS1 and PBS2 and Yersinia phage piR1-37, thymine has been replaced by uracil.JOURNAL, Kiljunen S, Hakala K, Pinta E, Huttunen S, Pluta P, Gador A, Lönnberg H, Skurnik M, Yersiniophage phiR1-37 is a tailed bacteriophage having a 270 kb DNA genome with thymidine replaced by deoxyuridine, Microbiology, 151, Pt 12, 4093–102, December 2005, 16339954, 10.1099/mic.0.28265-0, Another phage—Staphylococcal phage S6—has been identified with a genome where thymine has been replaced by uracil.JOURNAL, Uchiyama J, Takemura-Uchiyama I, Sakaguchi Y, Gamoh K, Kato S, Daibata M, Ujihara T, Misawa N, Matsuzaki S, Intragenus generalized transduction in Staphylococcus spp. by a novel giant phage, The ISME Journal, 8, 9, 1949–52, September 2014, 24599069, 10.1038/ismej.2014.29, 4139722, Uracil is also found in the DNA of Plasmodium falciparumMolnár P, Marton L, Izrael R, Pálinkás HL, Vértessy BG (2018) Uracil moieties in Plasmodium falciparum genomic DNA. FEBS Open Bio 8(11):1763–1772 It is present in relatively small amounts (7–10 uracil residues per million bases).5-hydroxymethyldeoxyuridine,(hm5dU) is also known to replace thymidine in several genomes including the Bacillus phages SPO1, ϕe, SP8, H1, 2C and SP82. Another modified uracil—5-dihydroxypentauracil—has also been described.Casella E, Markewych O, Dosmar M, Heman W (1978) Production and expression of dTMP-enriched DNA of bacteriophage SP15. J Virology 28 (3) 753–66Base J (beta-d-glucopyranosyloxymethyluracil), a modified form of uracil, is also found in several organisms: the flagellates Diplonema and Euglena, and all the kinetoplastid genera.JOURNAL, Simpson L, A base called J, Proceedings of the National Academy of Sciences of the United States of America, 95, 5, 2037–38, March 1998, 9482833, 33841, 10.1073/pnas.95.5.2037, 1998PNAS...95.2037S, Biosynthesis of J occurs in two steps: in the first step, a specific thymidine in DNA is converted into hydroxymethyldeoxyuridine; in the second, HOMedU is glycosylated to form J.JOURNAL, Borst P, Sabatini R, Base J: discovery, biosynthesis, and possible functions, Annual Review of Microbiology, 62, 235–51, 2008, 18729733, 10.1146/annurev.micro.62.081307.162750, Proteins that bind specifically to this base have been identified.JOURNAL, Cross M, Kieft R, Sabatini R, Wilm M, de Kort M, van der Marel GA, van Boom JH, van Leeuwen F, Borst P, The modified base J is the target for a novel DNA-binding protein in kinetoplastid protozoans, The EMBO Journal, 18, 22, 6573–81, November 1999, 10562569, 1171720, 10.1093/emboj/18.22.6573, JOURNAL, DiPaolo C, Kieft R, Cross M, Sabatini R, Regulation of trypanosome DNA glycosylation by a SWI2/SNF2-like protein, Molecular Cell, 17, 3, 441–51, February 2005, 15694344, 10.1016/j.molcel.2004.12.022, JOURNAL, Vainio S, Genest PA, ter Riet B, van Luenen H, Borst P, Evidence that J-binding protein 2 is a thymidine hydroxylase catalyzing the first step in the biosynthesis of DNA base J, Molecular and Biochemical Parasitology, 164, 2, 157–61, April 2009, 19114062, 10.1016/j.molbiopara.2008.12.001, These proteins appear to be distant relatives of the Tet1 oncogene that is involved in the pathogenesis of acute myeloid leukemia.JOURNAL, Iyer LM, Tahiliani M, Rao A, Aravind L, Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids, Cell Cycle, 8, 11, 1698–710, June 2009, 19411852, 2995806, 10.4161/cc.8.11.8580, J appears to act as a termination signal for RNA polymerase II.JOURNAL, van Luenen HG, Farris C, Jan S, Genest PA, Tripathi P, Velds A, Kerkhoven RM, Nieuwland M, Haydock A, Ramasamy G, Vainio S, Heidebrecht T, Perrakis A, Pagie L, van Steensel B, Myler PJ, Borst P, Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania, Cell, 150, 5, 909–21, August 2012, 22939620, 3684241, 10.1016/j.cell.2012.07.030, JOURNAL, Hazelbaker DZ, Buratowski S, Transcription: base J blocks the way, Current Biology, 22, 22, R960-2, November 2012, 23174300, 3648658, 10.1016/j.cub.2012.10.010, In 1976, the S-2La bacteriophage, which infects species of the genus Synechocystis, was found to have all the adenosine bases within its genome replaced by 2,6-diaminopurine.JOURNAL, Khudyakov IY, Kirnos MD, Alexandrushkina NI, Vanyushin BF, Cyanophage S-2L contains DNA with 2,6-diaminopurine substituted for adenine, Virology, 88, 1, 8–18, 1978, 676082, 10.1016/0042-6822(78)90104-6, In 2016 deoxyarchaeosine was found to be present in the genomes of several bacteria and the Escherichia phage 9g.JOURNAL, Thiaville JJ, Kellner SM, Yuan Y, Hutinet G, Thiaville PC, Jumpathong W, Mohapatra S, Brochier-Armanet C, Letarov AV, Hillebrand R, Malik CK, Rizzo CJ, Dedon PC, de Crécy-Lagard V, Novel genomic island modifies DNA with 7-deazaguanine derivatives, Proceedings of the National Academy of Sciences of the United States of America, 113, 11, E1452–59, 2016, 26929322, 4801273, 10.1073/pnas.1518570113, 2016PNAS..113E1452T, Modified bases also occur in DNA. The first of these recognised was 5-methylcytosine, which was found in the genome of Mycobacterium tuberculosis in 1925.JOURNAL, Johnson TB, Coghill RD, 1925, Pyrimidines. CIII. The discovery of 5-methylcytosine in tuberculinic acid, the nucleic acid of the tubercle bacillus., Journal of the American Chemical Society, 47, 2838–44, 10.1021/ja01688a030, The complete replacement of cytosine by 5-glycosylhydroxymethylcytosine in T even phages (T2, T4 and T6) was observed in 1953.JOURNAL, Wyatt GR, Cohen SS, The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine, The Biochemical Journal, 55, 5, 774–82, 1953, 13115372, 1269533, 10.1042/bj0550774, In the genomes of Xanthomonas oryzae bacteriophage Xp12 and halovirus FH the full complement of cystosine has been replaced by 5-methylcytosine.JOURNAL, Kuo TT, Huang TC, Teng MH, 5-Methylcytosine replacing cytosine in the deoxyribonucleic acid of a bacteriophage for Xanthomonas oryzae, Journal of Molecular Biology, 34, 2, 373–75, 1968, 5760463, 10.1016/0022-2836(68)90263-5, JOURNAL, Vogelsang-Wenke, Heike, Oesterhelt, Dieter, vanc, Isolation of a halobacterial phage with a fully cytosine-methylated genome, MGG Molecular & General Genetics, March 1988, 211, 3, 407–14, 10.1007/BF00425693, 6N-methyladenine was discovered to be present in DNA in 1955.JOURNAL, Dunn DB, Smith JD, Occurrence of a new base in the deoxyribonucleic acid of a strain of Bacterium coli, Nature, 175, 4451, 336–37, 1955, 13235889, 10.1038/175336a0, N6-carbamoyl-methyladenine was described in 1975.JOURNAL, Allet B, Bukhari AI, Analysis of bacteriophage mu and lambda-mu hybrid DNAs by specific endonucleases, Journal of Molecular Biology, 92, 4, 529–40, 1975, 1097703, 10.1016/0022-2836(75)90307-1, 7-Methylguanine was described in 1976.JOURNAL, Nikolskaya II, Lopatina NG, Debov SS, Methylated guanine derivative as a minor base in the DNA of phage DDVI Shigella dysenteriae, Biochimica et Biophysica Acta, 435, 2, 206–10, 1976, 779843, 10.1016/0005-2787(76)90251-3, N4-methylcytosine in DNA was described in 1983.JOURNAL, Janulaitis A, Klimasauskas S, Petrusyte M, Butkus V, Cytosine modification in DNA by BcnI methylase yields N4-methylcytosine, FEBS Letters, 161, 1, 131–34, 1983, 6884523, 10.1016/0014-5793(83)80745-5, In 1985 5-hydroxycytosine was found in the genomes of the Rhizobium phages RL38JI and N17.JOURNAL, Swinton D, Hattman S, Benzinger R, Buchanan-Wollaston V, Beringer J, Replacement of the deoxycytidine residues in Rhizobium bacteriophage RL38JI DNA, FEBS Letters, 184, 2, 294–98, 1985, 2987032, 10.1016/0014-5793(85)80625-6, α-putrescinylthymine occurs in both the genomes of the Delftia phage ΦW-14 and the Bacillus phage SP10.JOURNAL, Maltman KL, Neuhard J, Warren RA, 5-[(Hydroxymethyl)-O-pyrophosphoryl]uracil, an intermediate in the biosynthesis of alpha-putrescinylthymine in deoxyribonucleic acid of bacteriophage phi W-14, Biochemistry, 20, 12, 3586–91, 1981, 7260058, 10.1021/bi00515a043, α-glutamylthymidine is found in the Bacillus phage SP01 and 5-dihydroxypentyluracil is found in the Bacillus phage SP15.The reason for the presence of these non canonical bases in DNA is not known. It seems likely that at least part of the reason for their presence in bacterial viruses (phages) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses.This does not appear to be the entire story. Four modifications to the cytosine residues in human DNA have been reported.JOURNAL, Carell T, Kurz MQ, Müller M, Rossa M, Spada F, Non-canonical bases in the genome: The regulatory information layer in DNA, Angewandte Chemie (International Ed. in English), 57, 4296–4312, 2017, 28941008, 10.1002/anie.201708228, These modifications are the addition of methyl (CH3)-, hydroxymethyl (CH2OH)-, formyl (CHO)- and carboxyl (COOH)- groups. These modifications are thought to have regulatory functions.Uracil is found in the centromeric regions of at least two human chromosomes (chromosome 6 and chromosome 11).Shu X, Liu M, Lu Z, Zhu C, Meng H, Huang S, Zhang X, Yi C (2018) Genome-wide mapping reveals that deoxyuridine is enriched in the human centromeric DNA. Nat Chem Biol {{doi|10.1038/s41589-018-0065-9}}

Listing of non canonical bases found in DNA

Seventeen non canonical bases are known to occur in DNA. Most of these are modifications of the canonical bases plus uracil.
  • Modified Adenosine
    • N6-carbamoyl-methyladenine
    • N6-methyadenine
  • Modified Guanine
    • 7-Methylguanine
  • Modified Cytosine
    • N4-Methylcytosine
    • 5-Carboxylcytosine
    • 5-Formylcytosine
    • 5-Glycosylhydroxymethylcytosine
    • 5-Hydroxycytosine
    • 5-Methylcytosine
  • Modified Thymidine
    • α-Glutamythymidine
    • α-Putrescinylthymine
  • Uracil and modifications
    • Base J
    • Uracil
    • 5-Dihydroxypentauracil
    • 5-Hydroxymethyldeoxyuracil
  • Others
    • Deoxyarchaeosine
    • 2,6-Diaminopurine
File:DNA-ligand-by-Abalone.png|left|thumb|DNA major and minor grooves. The latter is a binding site for the Hoechst stainHoechst stain

Grooves

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. One groove, the major groove, is 22 angstroms (Ã…) wide and the other, the minor groove, is 12 Ã… wide.JOURNAL, Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, Dickerson RE, Crystal structure analysis of a complete turn of B-DNA, Nature, 287, 5784, 755–58, October 1980, 7432492, 10.1038/287755a0, 1980Natur.287..755W, The width of the major groove means that the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove.JOURNAL, Pabo CO, Sauer RT, Protein-DNA recognition, Annual Review of Biochemistry, 53, 293–321, 1984, 6236744, 10.1146/annurev.bi.53.070184.001453, This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

Base pairing

{{further|Base pair}}In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a Watson-Crick base pair. Another type of base pairing is Hoogsteen base pairing where two hydrogen bonds form between guanine and cytosine.JOURNAL, Nikolova EN, Zhou H, Gottardo FL, Alvey HS, Kimsey IJ, Al-Hashimi HM, A historical account of Hoogsteen base-pairs in duplex DNA, Biopolymers, 99, 12, 955–68, 2013, 23818176, 3844552, 10.1002/bip.22334, As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature.JOURNAL, Clausen-Schaumann H, Rief M, Tolksdorf C, Gaub HE, Mechanical stability of single DNA molecules, Biophysical Journal, 78, 4, 1997–2007, April 2000, 10733978, 1300792, 10.1016/S0006-3495(00)76747-6, 2000BpJ....78.1997C, As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms.{| border="0" border="0" cellpadding="2" cellspacing="0" style="width:230px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
282px)
{| border="0" border="0" cellpadding="2" cellspacing="0" style="width:230px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
282px)
Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right).DNA with high GC-content is more stable than DNA with low GC-content.{{Anchor|ssDNA}}As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands.JOURNAL, Chalikian TV, Völker J, Plum GE, Breslauer KJ, A more unified picture for the thermodynamics of nucleic acid duplex melting: a characterization by calorimetric and volumetric techniques, Proceedings of the National Academy of Sciences of the United States of America, 96, 14, 7853–58, July 1999, 10393911, 22151, 10.1073/pnas.96.14.7853, 1999PNAS...96.7853C, In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.JOURNAL, deHaseth PL, Helmann JD, Open complex formation by Escherichia coli RNA polymerase: the mechanism of polymerase-induced strand separation of double helical DNA, Molecular Microbiology, 16, 5, 817–24, June 1995, 7476180, 10.1111/j.1365-2958.1995.tb02309.x, In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.JOURNAL, Isaksson J, Acharya S, Barman J, Cheruku P, Chattopadhyaya J, Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern, Biochemistry, 43, 51, 15996–6010, December 2004, 15609994, 10.1021/bi048221v,weblink no,weblink" title="web.archive.org/web/20070610205112weblink">weblink 10 June 2007, dmy-all,

Sense and antisense

{{further|Sense (molecular biology)}}A DNA sequence is called a "sense" sequence if it is the same as that of a messenger RNA copy that is translated into protein.Designation of the two strands of DNA {{Webarchive|url=https://web.archive.org/web/20080424015915weblink |date=24 April 2008 }} JCBN/NC-IUB Newsletter 1989. Retrieved 7 May 2008
The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear.JOURNAL, Hüttenhofer A, Schattner P, Polacek N, Non-coding RNAs: hope or hype?, Trends in Genetics, 21, 5, 289–97, May 2005, 15851066, 10.1016/j.tig.2005.03.007, One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.JOURNAL, Munroe SH, Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns, Journal of Cellular Biochemistry, 93, 4, 664–71, November 2004, 15389973, 10.1002/jcb.20252,
A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes.JOURNAL, Makalowska I, Lin CF, Makalowski W, Overlapping genes in vertebrate genomes, Computational Biology and Chemistry, 29, 1, 1–12, February 2005, 15680581, 10.1016/j.compbiolchem.2004.12.006, In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription,JOURNAL, Johnson ZI, Chisholm SW, Properties of overlapping genes are conserved across microbial genomes, Genome Research, 14, 11, 2268–72, November 2004, 15520290, 525685, 10.1101/gr.2433104, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.JOURNAL, Lamb RA, Horvath CM, Diversity of coding strategies in influenza viruses, Trends in Genetics, 7, 8, 261–66, August 1991, 1771674, 10.1016/0168-9525(91)90326-L,

Supercoiling

{{further|DNA supercoil}}DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.JOURNAL, Benham CJ, Mielke SP, DNA mechanics, Annual Review of Biomedical Engineering, 7, 21–53, 2005, 16004565, 10.1146/annurev.bioeng.6.062403.132016, If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases.JOURNAL, Champoux JJ, DNA topoisomerases: structure, function, and mechanism, Annual Review of Biochemistry, 70, 369–413, 2001, 11395412, 10.1146/annurev.biochem.70.1.369, These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.JOURNAL, Wang JC, Cellular roles of DNA topoisomerases: a molecular perspective, Nature Reviews Molecular Cell Biology, 3, 6, 430–40, June 2002, 12042765, 10.1038/nrm831, (File:A-DNA, B-DNA and Z-DNA.png|thumb|right|From left to right, the structures of A, B and Z DNA)

Alternative DNA structures

{{further|Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid|Molecular models of DNA|DNA structure}}DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, and the presence of polyamines in solution.JOURNAL, Basu HS, Feuerstein BG, Zarling DA, Shafer RH, Marton LJ, Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies, Journal of Biomolecular Structure & Dynamics, 6, 2, 299–309, October 1988, 2482766, 10.1080/07391102.1988.10507714, The first published reports of A-DNA X-ray diffraction patterns—and also B-DNA—used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA.JOURNAL, Franklin RE, Gosling RG, The Structure of Sodium Thymonucleate Fibres I. The Influence of Water Content, Acta Crystallogr, 6, 8–9, 673–77, 6 March 1953, 10.1107/S0365110X53001939,weblink no,weblink" title="web.archive.org/web/20160109043915weblink">weblink 9 January 2016, JOURNAL, Franklin RE, Gosling RG, The structure of sodium thymonucleate fibres. II. The cylindrically symmetrical Patterson function, Acta Crystallogr, 6, 8–9, 678–85, 1953, 10.1107/S0365110X53001940, JOURNAL, Franklin RE, Gosling RG, Molecular configuration in sodium thymonucleate, Nature, 171, 4356, 740–41, April 1953, 13054694, 10.1038/171740a0,weblink PDF, 1953Natur.171..740F, no,weblink" title="web.archive.org/web/20110103160712weblink">weblink 3 January 2011, dmy-all, An alternative analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions.JOURNAL, Wilkins MH, Stokes AR, Wilson HR, Molecular structure of deoxypentose nucleic acids, Nature, 171, 4356, 738–40, April 1953, 13054693, 10.1038/171738a0,weblink PDF, 1953Natur.171..738W, no,weblink" title="web.archive.org/web/20110513234223weblink">weblink 13 May 2011, dmy-all, In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.Although the B-DNA form is most common under the conditions found in cells,JOURNAL, Leslie AG, Arnott S, Chandrasekaran R, Ratliff RL, Polymorphism of DNA double helices, Journal of Molecular Biology, 143, 1, 49–72, October 1980, 7441761, 10.1016/0022-2836(80)90124-2, it is not a well-defined conformation but a family of related DNA conformationsJOURNAL, Baianu IC, 1980, Structural Order and Partial Disorder in Biological systems,weblink Bull. Math. Biol., 42, 4, 137–41, 10.1007/BF02462372, that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.BOOK, Hosemann R, Bagchi RN, Direct analysis of diffraction by matter, North-Holland Publishers, Amsterdam â€“ New York, 1962, JOURNAL, Baianu IC, X-ray scattering by partially disordered membrane systems, Acta Crystallogr A, 34, 5, 751–53, 1978, 10.1107/S0567739478001540, 1978AcCrA..34..751B, Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes.JOURNAL, Wahl MC, Sundaralingam M, Crystal structures of A-DNA duplexes, Biopolymers, 44, 1, 45–63, 1997, 9097733, 10.1002/(SICI)1097-0282(1997)44:13.0.CO;2-#, JOURNAL, Lu XJ, Shakked Z, Olson WK, A-form conformational motifs in ligand-bound DNA structures, Journal of Molecular Biology, 300, 4, 819–40, July 2000, 10891271, 10.1006/jmbi.2000.3690, Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form.JOURNAL, Rothenburg S, Koch-Nolte F, Haag F, DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles, Immunological Reviews, 184, 286–98, December 2001, 12086319, 10.1034/j.1600-065x.2001.1840125.x, These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.JOURNAL, Oh DB, Kim YG, Rich A, Z-DNA-binding proteins can act as potent effectors of gene expression in vivo, Proceedings of the National Academy of Sciences of the United States of America, 99, 26, 16666–71, December 2002, 12486233, 139201, 10.1073/pnas.262672699, 2002PNAS...9916666O,

Alternative DNA chemistry

For many years, exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1, was announced,NEWS, Jason, Palmer, vanc, Arsenic-loving bacteria may help in hunt for alien life, 2 December 2010,weblink BBC News, 2 December 2010, no,weblink" title="web.archive.org/web/20101203045804weblink">weblink 3 December 2010, NEWS, Bortman, Henry, Arsenic-Eating Bacteria Opens New Possibilities for Alien Life, 2 December 2010,weblink Space.com, 2 December 2010, no,weblink" title="web.archive.org/web/20101204235915weblink">weblink 4 December 2010, though the research was disputed,JOURNAL, Katsnelson, Alla, vanc, Arsenic-eating microbe may redefine chemistry of life, 2 December 2010,weblink Nature News, 10.1038/news.2010.645, no,weblink" title="web.archive.org/web/20120212155007weblink">weblink 12 February 2012, and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.JOURNAL, Cressey, Daniel, vanc, 'Arsenic-life' Bacterium Prefers Phosphorus after all, 3 October 2012, Nature News, 10.1038/nature.2012.11520,

Quadruplex structures

{{further|G-quadruplex}}At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes.JOURNAL, Greider CW, Blackburn EH, Identification of a specific telomere terminal transferase activity in Tetrahymena extracts, Cell, 43, 2 Pt 1, 405–13, December 1985, 3907856, 10.1016/0092-8674(85)90170-9, These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected.JOURNAL, Nugent CI, Lundblad V, The telomerase reverse transcriptase: components and regulation, Genes & Development, 12, 8, 1073–85, April 1998, 9553037, 10.1101/gad.12.8.1073, In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.JOURNAL, Wright WE, Tesmer VM, Huffman KE, Levene SD, Shay JW, Normal human chromosomes have long G-rich telomeric overhangs at one end, Genes & Development, 11, 21, 2801–09, November 1997, 9353250, 316649, 10.1101/gad.11.21.2801, File:Parallel telomere quadruple.png|thumb|right|DNA quadruplex formed by (telomere]] repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix. The green spheres in the center represent potassium ions.Created from {{webarchive|url=https://web.archive.org/web/20161017192637weblink |date=17 October 2016 }})These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure.JOURNAL, Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S, Quadruplex DNA: sequence, topology and structure, Nucleic Acids Research, 34, 19, 5402–15, 2006, 17012276, 1636468, 10.1093/nar/gkl655, These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit.JOURNAL, Parkinson GN, Lee MP, Neidle S, Crystal structure of parallel quadruplexes from human telomeric DNA, Nature, 417, 6891, 876–80, June 2002, 12050675, 10.1038/nature755, 2002Natur.417..876P, Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins.JOURNAL, Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T, Mammalian telomeres end in a large duplex loop, Cell, 97, 4, 503–14, May 1999, 10338214, 10.1016/S0092-8674(00)80760-6, At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.{| border="0" border="0" cellpadding="2" cellspacing="0" style="width:200px; font-size:85%; border:1px solid #ccc; margin:0.3em;"95px)95px)
Single branchMultiple branches
Branched DNA can form networks containing multiple branches.

Branched DNA

{{further|Branched DNA|DNA nanotechnology}}In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible.JOURNAL, Seeman NC, DNA enables nanoscale control of the structure of matter, Quarterly Reviews of Biophysics, 38, 4, 363–71, November 2005, 16515737, 3478329, 10.1017/S0033583505004087, Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

Artificial bases

Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named Hachimoji DNA. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence implies that there is nothing special about the four natural nucleobases that evolved on Earth.JOURNAL, Matthew, Warren, vanc, Four new DNA letters double life’s alphabet, Nature, 21 February 2019, 10.1038/d41586-019-00650-8, 566, 436, JOURNAL, Hoshika S, Leal NA, Kim MJ, Kim MS, Karalkar NB, Kim HJ, Bates AM, Watkins NE, SantaLucia HA, Meyer AJ, DasGupta S, Piccirilli JA, Ellington AD, SantaLucia J, Georgiadis MM, Benner SA, 6, Hachimoji DNA and RNA: A genetic system with eight building blocks (paywall),weblink Science (journal), Science, 363, 6429, 884–887, 22 February 2019, 10.1126/science.aat0971, 24 February 2019,

Chemical modifications and altered DNA packaging

{| border="0" border="0" cellpadding="2" cellspacing="0" style="width:300px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
75px)95px)97px)
cytosine5-methylcytosinethymine
Structure of cytosine with and without the 5-methyl group. Deamination converts 5-methylcytosine into thymine.

Base modifications and DNA packaging

{{further|DNA methylation|Chromatin remodeling}}The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.JOURNAL, Hu Q, Rosenfeld MG, Epigenetic regulation of human embryonic stem cells, Frontiers in Genetics, 3, 238, 2012, 23133442, 3488762, 10.3389/fgene.2012.00238, For one example, cytosine methylation produces 5-methylcytosine, which is important for X-inactivation of chromosomes.JOURNAL, Klose RJ, Bird AP, Genomic DNA methylation: the mark and its mediators, Trends in Biochemical Sciences, 31, 2, 89–97, February 2006, 16403636, 10.1016/j.tibs.2005.12.008, The average level of methylation varies between organisms—the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine.JOURNAL, Bird A, DNA methylation patterns and epigenetic memory, Genes & Development, 16, 1, 6–21, January 2002, 11782440, 10.1101/gad.947102, Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations.JOURNAL, Walsh CP, Xu GL, Cytosine methylation and DNA repair, Current Topics in Microbiology and Immunology, 301, 283–315, 2006, 16570853, 10.1007/3-540-31390-7_11, 3-540-29114-8, Current Topics in Microbiology and Immunology, Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain,JOURNAL, Kriaucionis S, Heintz N, The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain, Science, 324, 5929, 929–30, May 2009, 19372393, 3263819, 10.1126/science.1169786, 2009Sci...324..929K, and the glycosylation of uracil to produce the "J-base" in kinetoplastids.JOURNAL, Ratel D, Ravanat JL, Berger F, Wion D, N6-methyladenine: the other methylated base of DNA, BioEssays, 28, 3, 309–15, March 2006, 16479578, 2754416, 10.1002/bies.20342, JOURNAL, Gommers-Ampt JH, Van Leeuwen F, de Beer AL, Vliegenthart JF, Dizdaroglu M, Kowalak JA, Crain PF, Borst P, beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei, Cell, 75, 6, 1129–36, December 1993, 8261512, 10.1016/0092-8674(93)90322-H,

Damage

{{further|DNA damage (naturally occurring)|Mutation|DNA damage theory of aging}}File:Benzopyrene DNA adduct 1JDG.png|thumb|right|A covalent adduct between a metabolically activated form of benzo[a]pyrene, the major mutagen in (tobacco smoking|tobacco smoke]], and DNACreated from PDB 1JDG)DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases.JOURNAL, Douki T, Reynaud-Angelin A, Cadet J, Sage E, Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation, Biochemistry, 42, 30, 9221–26, August 2003, 12885257, 10.1021/bi034593c, On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks.JOURNAL, Cadet J, Delatour T, Douki T, Gasparutto D, Pouget JP, Ravanat JL, Sauvaigo S, Hydroxyl radicals and DNA base damage, Mutation Research, 424, 1–2, 9–21, March 1999, 10064846, 10.1016/S0027-5107(99)00004-4, A typical human cell contains about 150,000 bases that have suffered oxidative damage.JOURNAL, Beckman KB, Ames BN, Oxidative decay of DNA, The Journal of Biological Chemistry, 272, 32, 19633–36, August 1997, 9289489, 10.1074/jbc.272.32.19633, Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations.JOURNAL, Valerie K, Povirk LF, Regulation and mechanisms of mammalian double-strand break repair, Oncogene, 22, 37, 5792–812, September 2003, 12947387, 10.1038/sj.onc.1206679, These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.NEWS,weblink Unearthing Prehistoric Tumors, and Debate, The New York Times, 28 December 2010, Johnson, George, vanc, "If we lived long enough, sooner or later we all would get cancer.", no,weblink" title="web.archive.org/web/20170624233156weblink">weblink 24 June 2017, dmy-all, BOOK, Alberts B, Johnson A, Lewis J, Molecular biology of the cell, Garland Science, New York, 2002, 4th, The Preventable Causes of Cancer, 0-8153-4072-9,weblink A certain irreducible background incidence of cancer is to be expected regardless of circumstances: mutations can never be absolutely avoided, because they are an inescapable consequence of fundamental limitations on the accuracy of DNA replication, as discussed in Chapter 5. If a human could live long enough, it is inevitable that at least one of his or her cells would eventually accumulate a set of mutations sufficient for cancer to develop., etal, no,weblink" title="web.archive.org/web/20160102193148weblink">weblink 2 January 2016, dmy-all, DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.BOOK, Kimura, Honoka, Suzuki, Aoi, vanc, New Research on DNA Damage, 2008, Nova Science Publishers, New York, 978-1-60456-581-2, Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K, Cancer and aging as consequences of un-repaired DNA damage,weblink 1–47., no,weblink 25 October 2014, dmy-all, JOURNAL, Hoeijmakers JH, DNA damage, aging, and cancer, The New England Journal of Medicine, 361, 15, 1475–85, October 2009, 19812404, 10.1056/NEJMra0804615, JOURNAL, Freitas AA, de Magalhães JP, A review and appraisal of the DNA damage theory of ageing, Mutation Research, 728, 1–2, 12–22, 2011, 21600302, 10.1016/j.mrrev.2011.05.001, Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations.JOURNAL, Ferguson LR, Denny WA, The genetic toxicology of acridines, Mutation Research, 258, 2, 123–60, September 1991, 1881402, 10.1016/0165-1110(91)90006-H, As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen.JOURNAL, Stephens TD, Bunde CJ, Fillmore BJ, Mechanism of action in thalidomide teratogenesis, Biochemical Pharmacology, 59, 12, 1489–99, June 2000, 10799645, 10.1016/S0006-2952(99)00388-3, Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication.JOURNAL, Jeffrey AM, DNA modification by chemical carcinogens, Pharmacology & Therapeutics, 28, 2, 237–72, 1985, 3936066, 10.1016/0163-7258(85)90013-0, Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.JOURNAL, Braña MF, Cacho M, Gradillas A, de Pascual-Teresa B, Ramos A, Intercalators as anticancer drugs, Current Pharmaceutical Design, 7, 17, 1745–80, November 2001, 11562309, 10.2174/1381612013397113,

Biological functions

File:Eukaryote DNA-en.svg|thumb|upright=1.45|Location of eukaryote nuclear DNAnuclear DNADNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.

Genes and genomes

{{further|Cell nucleus|Chromatin|Chromosome|Gene|Noncoding DNA}}Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid.JOURNAL, Thanbichler M, Wang SC, Shapiro L, The bacterial nucleoid: a highly organized and dynamic structure, Journal of Cellular Biochemistry, 96, 3, 506–21, October 2005, 15988757, 10.1002/jcb.20519, The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which control transcription of the open reading frame.In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences.JOURNAL, Wolfsberg TG, McEntyre J, Schuler GD, Guide to the draft human genome, Nature, 409, 6822, 824–26, February 2001, 11236998, 10.1038/35057000, 2001Natur.409..824W, The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species, represent a long-standing puzzle known as the "C-value enigma".JOURNAL, Gregory TR, The C-value enigma in plants and animals: a review of parallels and an appeal for partnership, Annals of Botany, 95, 1, 133–46, January 2005, 15596463, 10.1093/aob/mci009, 4246714, However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.File:T7 RNA polymerase.jpg|thumb|T7 RNA polymerase (blue) producing an (Messenger RNA|mRNA]] (green) from a DNA template (orange)Created from PDB 1MSW {{webarchive|url=https://web.archive.org/web/20080106154019weblink |date=6 January 2008 }})Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes.JOURNAL, Pidoux AL, Allshire RC, The role of heterochromatin in centromere function, Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 360, 1455, 569–79, March 2005, 15905142, 1569473, 10.1098/rstb.2004.1611, An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation.JOURNAL, Harrison PM, Hegyi H, Balasubramanian S, Luscombe NM, Bertone P, Echols N, Johnson T, Gerstein M, Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22, Genome Research, 12, 2, 272–80, February 2002, 11827946, 155275, 10.1101/gr.207102, These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.JOURNAL, Harrison PM, Gerstein M, Studying genomes through the aeons: protein families, pseudogenes and proteome evolution, Journal of Molecular Biology, 318, 5, 1155–74, May 2002, 12083509, 10.1016/S0022-2836(02)00109-2,

Transcription and translation

{{further|Genetic code|Transcription (genetics)|Protein biosynthesis}}A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA, and TAG codons.File:DNA replication en.svg|thumb|upright=2.05|right|DNA replication. The double helix is unwound by a helicase and topoisomerase. Next, one DNA polymerase produces the leading strand copy. Another DNA polymerase binds to the lagging strand. This enzyme makes discontinuous segments (called Okazaki fragments) before DNA ligaseDNA ligase

Replication

{{further|DNA replication}}Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix.JOURNAL, Albà M, Replicative DNA polymerases, Genome Biology, 2, 1, REVIEWS3002, 2001, 11178285, 150442, 10.1186/gb-2001-2-1-reviews3002, true, In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

Extracellular nucleic acids

Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L.BOOK, Tani, Katsuji, Nasu, Masao, Kikuchi, Yo, Rykova, Elena Y., vanc, Extracellular Nucleic Acids, Springer, 2010, 25–38, Roles of Extracellular DNA in Bacterial Ecosystems, 978-3-642-12616-1, Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer;JOURNAL, Vlassov VV, Laktionov PP, Rykova EY, Extracellular nucleic acids, BioEssays, 29, 7, 654–67, July 2007, 17563084, 10.1002/bies.20604, it may provide nutrients;JOURNAL, Finkel SE, Kolter R, DNA as a nutrient: novel role for bacterial competence gene homologs, Journal of Bacteriology, 183, 21, 6288–93, November 2001, 11591672, 100116, 10.1128/JB.183.21.6288-6293.2001, and it may act as a buffer to recruit or titrate ions or antibiotics.JOURNAL, Mulcahy H, Charron-Mazenod L, Lewenza S, Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms, PLoS Pathogens, 4, 11, e1000213, November 2008, 19023416, 2581603, 10.1371/journal.ppat.1000213, Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm;JOURNAL, Berne C, Kysela DT, Brun YV, A bacterial extracellular DNA inhibits settling of motile progeny cells within a biofilm, Molecular Microbiology, 77, 4, 815–29, August 2010, 20598083, 2962764, 10.1111/j.1365-2958.2010.07267.x, it may contribute to biofilm formation;JOURNAL, Whitchurch CB, Tolker-Nielsen T, Ragas PC, Mattick JS, Extracellular DNA required for bacterial biofilm formation, Science, 295, 5559, 1487, February 2002, 11859186, 10.1126/science.295.5559.1487, and it may contribute to the biofilm's physical strength and resistance to biological stress.JOURNAL, Hu W, Li L, Sharma S, Wang J, McHardy I, Lux R, Yang Z, He X, Gimzewski JK, Li Y, Shi W, DNA builds and strengthens the extracellular matrix in Myxococcus xanthus biofilms by interacting with exopolysaccharides, PLOS ONE, 7, 12, e51905, 2012, 23300576, 3530553, 10.1371/journal.pone.0051905, 2012PLoSO...751905H, Cell-free fetal DNA is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus.JOURNAL, Hui L, Bianchi DW, Recent advances in the prenatal interrogation of the human fetal genome, Trends in Genetics, 29, 2, 84–91, February 2013, 23158400, 4378900, 10.1016/j.tig.2012.10.013,

Interactions with proteins

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

DNA-binding proteins

{{further|DNA-binding protein}}{| border="0" border="0" cellpadding="0" cellspacing="0" style="width:260px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
260px)
|
Interaction of DNA (in orange) with histones (in blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA.Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved.JOURNAL, Sandman K, Pereira SL, Reeve JN, Diversity of prokaryotic chromosomal proteins and the origin of the nucleosome, Cellular and Molecular Life Sciences, 54, 12, 1350–64, December 1998, 9893710, 10.1007/s000180050259, JOURNAL, Dame RT, The role of nucleoid-associated proteins in the organization and compaction of bacterial chromatin, Molecular Microbiology, 56, 4, 858–70, May 2005, 15853876, 10.1111/j.1365-2958.2005.04598.x, The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence.JOURNAL, Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ, Crystal structure of the nucleosome core particle at 2.8 A resolution, Nature, 389, 6648, 251–60, September 1997, 9305837, 10.1038/38444, 1997Natur.389..251L, Chemical modifications of these basic amino acid residues include methylation, phosphorylation, and acetylation.JOURNAL, Jenuwein T, Allis CD, Translating the histone code, Science, 293, 5532, 1074–80, August 2001, 11498575, 10.1126/science.1063127,weblink no,weblink" title="web.archive.org/web/20170808142426weblink">weblink 8 August 2017, dmy-all, These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.JOURNAL, Ito T, Nucleosome assembly and remodeling, Current Topics in Microbiology and Immunology, 274, 1–22, 2003, 12596902, 10.1007/978-3-642-55747-7_1, 978-3-540-44208-0, Current Topics in Microbiology and Immunology, Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.JOURNAL, Thomas JO, HMG1 and 2: architectural DNA-binding proteins, Biochemical Society Transactions, 29, Pt 4, 395–401, August 2001, 11497996, 10.1042/BST0290395, These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.JOURNAL, Grosschedl R, Giese K, Pagel J, HMG domain proteins: architectural elements in the assembly of nucleoprotein structures, Trends in Genetics, 10, 3, 94–100, March 1994, 8178371, 10.1016/0168-9525(94)90232-1, A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair.JOURNAL, Iftode C, Daniely Y, Borowiec JA, Replication protein A (RPA): the eukaryotic SSB, Critical Reviews in Biochemistry and Molecular Biology, 34, 3, 141–80, 1999, 10473346, 10.1080/10409239991209255, These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.File:Lambda repressor 1LMB.png|thumb|upright|The lambda repressor (helix-turn-helix]] transcription factor bound to its DNA targetCreated from PDB 1LMB {{webarchive|url=https://web.archive.org/web/20080106153949weblink |date=6 January 2008 }})In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.JOURNAL, Myers LC, Kornberg RD, Mediator of transcriptional regulation, Annual Review of Biochemistry, 69, 729–49, 2000, 10966474, 10.1146/annurev.biochem.69.1.729, Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.JOURNAL, Spiegelman BM, Heinrich R, Biological control through regulated transcriptional coactivators, Cell, 119, 2, 157–67, October 2004, 15479634, 10.1016/j.cell.2004.09.037, As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.JOURNAL, Li Z, Van Calcar S, Qu C, Cavenee WK, Zhang MQ, Ren B, A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells, Proceedings of the National Academy of Sciences of the United States of America, 100, 14, 8164–69, July 2003, 12808131, 166200, 10.1073/pnas.1332764100, 2003PNAS..100.8164L, Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.File:EcoRV 1RVA.png|thumb|left|The restriction enzyme (EcoRV]] (green) in a complex with its substrate DNACreated from PDB 1RVA {{webarchive|url=https://web.archive.org/web/20080106154027weblink |date=6 January 2008 }})

DNA-modifying enzymes

Nucleases and ligases

Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5′-GATATC-3′ and makes a cut at the horizontal line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system.JOURNAL, Bickle TA, Krüger DH, Biology of DNA restriction, Microbiological Reviews, 57, 2, 434–50, June 1993, 8336674, 372918, In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.Enzymes called DNA ligases can rejoin cut or broken DNA strands.JOURNAL, Doherty AJ, Suh SW, Structural and mechanistic conservation in DNA ligases, Nucleic Acids Research, 28, 21, 4051–58, November 2000, 11058099, 113121, 10.1093/nar/28.21.4051, Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.

Topoisomerases and helicases

Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break. Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.JOURNAL, Schoeffler AJ, Berger JM, Recent advances in understanding structure-function relationships in the type II topoisomerase mechanism, Biochemical Society Transactions, 33, Pt 6, 1465–70, December 2005, 16246147, 10.1042/BST20051465, Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands.JOURNAL, Tuteja N, Tuteja R, Unraveling DNA helicases. Motif, structure, mechanism and function, European Journal of Biochemistry, 271, 10, 1849–63, May 2004, 15128295, 10.1111/j.1432-1033.2004.04094.x, These enzymes are essential for most processes where enzymes need to access the DNA bases.

Polymerases

Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products is created based on existing polynucleotide chains—which are called templates. These enzymes function by repeatedly adding a nucleotide to the 3′ hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5′ to 3′ direction.JOURNAL, Joyce CM, Steitz TA, Polymerase structures and function: variations on a theme?, Journal of Bacteriology, 177, 22, 6321–29, November 1995, 7592405, 177480, 10.1128/jb.177.22.6321-6329.1995, In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ exonuclease activity is activated and the incorrect base removed.JOURNAL, Hubscher U, Maga G, Spadari S, Eukaryotic DNA polymerases, Annual Review of Biochemistry, 71, 133–63, 2002, 12045093, 10.1146/annurev.biochem.71.090501.150041, In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.JOURNAL, Johnson A, O'Donnell M, Cellular DNA replicases: components and dynamics at the replication fork, Annual Review of Biochemistry, 74, 283–315, 2005, 15952889, 10.1146/annurev.biochem.73.011303.073859, RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres.JOURNAL, Tarrago-Litvak L, Andréola ML, Nevinsky GA, Sarih-Cottin L, Litvak S, The reverse transcriptase of HIV-1: from enzymology to therapeutic intervention, FASEB Journal, 8, 8, 497–503, May 1994, 7514143, For example, HIV reverse transcriptase is an enzyme for AIDS virus replication. Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. It synthesizes telomeres at the ends of chromosomes. Telomeres prevent fusion of the ends of neighboring chromosomes and protect chromosome ends from damage.Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.JOURNAL, Martinez E, Multi-protein complexes in eukaryotic gene transcription, Plant Molecular Biology, 50, 6, 925–47, December 2002, 12516863, 10.1023/A:1021258713850,

Genetic recombination

{| border="0" border="0" cellpadding="0" cellspacing="0" style="width:250px; font-size:85%; border:1px solid #ccc; margin:0.3em;"
250px)
250px)
Structure of the Holliday junction intermediate in genetic recombination. The four separate DNA strands are coloured red, blue, green and yellow.Created from PDB 1M6G {{webarchive|url=https://web.archive.org/web/20100110012504weblink |date=10 January 2010 }}{{further|Genetic recombination}}(File:Chromosomal Recombination.svg|thumb|upright=1.15|left|Recombination involves the breaking and rejoining of two chromosomes (M and F) to produce two rearranged chromosomes (C1 and C2).)A DNA helix usually does not interact with other segments of DNA, and in human cells, the different chromosomes even occupy separate areas in the nucleus called "chromosome territories".JOURNAL, Cremer T, Cremer C, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nature Reviews Genetics, 2, 4, 292–301, April 2001, 11283701, 10.1038/35066075, This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins.JOURNAL, Pál C, Papp B, Lercher MJ, An integrated view of protein evolution, Nature Reviews Genetics, 7, 5, 337–48, May 2006, 16619049, 10.1038/nrg1838, Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.JOURNAL, O'Driscoll M, Jeggo PA, The role of double-strand break repair – insights from human genetics, Nature Reviews Genetics, 7, 1, 45–54, January 2006, 16369571, 10.1038/nrg1746, The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51.JOURNAL, Vispé S, Defais M, Mammalian Rad51 protein: a RecA homologue with pleiotropic functions, Biochimie, 79, 9–10, 587–92, October 1997, 9466696, 10.1016/S0300-9084(97)82007-X, The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA.JOURNAL, Neale MJ, Keeney S, Clarifying the mechanics of DNA strand exchange in meiotic recombination, Nature, 442, 7099, 153–58, July 2006, 16838012, 10.1038/nature04885, 2006Natur.442..153N, 5607947, A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.JOURNAL, Dickman MJ, Ingleston SM, Sedelnikova SE, Rafferty JB, Lloyd RG, Grasby JA, Hornby DP, The RuvABC resolvasome, European Journal of Biochemistry, 269, 22, 5492–501, November 2002, 12423347, 10.1046/j.1432-1033.2002.03250.x, Only strands of like polarity exchange DNA during recombination. There are two types of cleavage: east-west cleavage and north-south cleavage. The north-south cleavage nicks both strands of DNA, while the east-west cleavage has one strand of DNA intact. The formation of a Holliday junction during recombination makes it possible for genetic diversity, genes to exchange on chromosomes, and expression of wild-type viral genomes.

Evolution

{{further|RNA world hypothesis}}DNA contains the genetic information that allows all forms of life to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material.JOURNAL, Joyce GF, The antiquity of RNA-based evolution, Nature, 418, 6894, 214–21, July 2002, 12110897, 10.1038/418214a, 2002Natur.418..214J, JOURNAL, Orgel LE, Prebiotic chemistry and the origin of the RNA world, Critical Reviews in Biochemistry and Molecular Biology, 39, 2, 99–123, 2004, 15217990, 10.1080/10409230490460765, RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes.JOURNAL, Davenport RJ, Ribozymes. Making copies in the RNA world, Science, 292, 5520, 1278, May 2001, 11360970, 10.1126/science.292.5520.1278a, This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes.JOURNAL, Szathmáry E, What is the optimum size for the genetic alphabet?, Proceedings of the National Academy of Sciences of the United States of America, 89, 7, 2614–18, April 1992, 1372984, 48712, 10.1073/pnas.89.7.2614, 1992PNAS...89.2614S, However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution.JOURNAL, Lindahl T, Instability and decay of the primary structure of DNA, Nature, 362, 6422, 709–15, April 1993, 8469282, 10.1038/362709a0, 1993Natur.362..709L, Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old,JOURNAL, Vreeland RH, Rosenzweig WD, Powers DW, Isolation of a 250 million-year-old halotolerant bacterium from a primary salt crystal, Nature, 407, 6806, 897–900, October 2000, 11057666, 10.1038/35038060, 2000Natur.407..897V, but these claims are controversial.JOURNAL, Hebsgaard MB, Phillips MJ, Willerslev E, Geologically ancient DNA: fact or artefact?, Trends in Microbiology, 13, 5, 212–20, May 2005, 15866038, 10.1016/j.tim.2005.03.010, JOURNAL, Nickle DC, Learn GH, Rain MW, Mullins JI, Mittler JE, Curiously modern DNA for a "250 million-year-old" bacterium, Journal of Molecular Evolution, 54, 1, 134–37, January 2002, 11734907, 10.1007/s00239-001-0025-x, 2002JMolE..54..134N, Building blocks of DNA (adenine, guanine, and related organic molecules) may have been formed extraterrestrially in outer space.JOURNAL, Callahan MP, Smith KE, Cleaves HJ, Ruzicka J, Stern JC, Glavin DP, House CH, Dworkin JP, Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases, Proceedings of the National Academy of Sciences of the United States of America, 108, 34, 13995–98, August 2011, 21836052, 3161613, 10.1073/pnas.1106493108, 2011PNAS..10813995C, WEB, Steigerwald, John, vanc, NASA Researchers: DNA Building Blocks Can Be Made in Space,weblink NASA, 8 August 2011, 10 August 2011, no,weblink" title="web.archive.org/web/20150623004556weblink">weblink 23 June 2015, WEB, ScienceDaily Staff, DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests,weblink 9 August 2011, ScienceDaily, 9 August 2011, no,weblink 5 September 2011, Complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have also been formed in the laboratory under conditions mimicking those found in outer space, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar cosmic dust and gas clouds.WEB, Marlaire, Ruth, vanc, NASA Ames Reproduces the Building Blocks of Life in Laboratory,weblink 3 March 2015, NASA, 5 March 2015, no,weblink" title="web.archive.org/web/20150305083306weblink">weblink 5 March 2015,

Uses in technology

Genetic engineering

{{further|Molecular biology|Nucleic acid methods|Genetic engineering}}Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector.JOURNAL, Goff SP, Berg P, Construction of hybrid viruses containing SV40 and lambda phage DNA segments and their propagation in cultured monkey cells, Cell, 9, 4 PT 2, 695–705, December 1976, 189942, 10.1016/0092-8674(76)90133-1, The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research,JOURNAL, Houdebine LM, Transgenic animal models in biomedical research, Methods in Molecular Biology, 360, 163–202, 2007, 17172731, 10.1385/1-59745-165-7:163, 1-59745-165-7, or be grown in agriculture.JOURNAL, Daniell H, Dhingra A, Multigene engineering: dawn of an exciting new era in biotechnology, Current Opinion in Biotechnology, 13, 2, 136–41, April 2002, 11950565, 3481857, 10.1016/S0958-1669(02)00297-5, JOURNAL, Job D, Plant biotechnology in agriculture, Biochimie, 84, 11, 1105–10, November 2002, 12595138, 10.1016/S0300-9084(02)00013-5,

DNA profiling

{{further|DNA profiling}}Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator.NEWS,weblink From the crime scene to the courtroom: the journey of a DNA sample, Curtis, Caitlin, Hereward, James, vanc, 29 August 2017, The Conversation, 22 October 2017,weblink" title="web.archive.org/web/20171022033110weblink">weblink 22 October 2017, no, This process is formally termed DNA profiling, also called DNA fingerprinting. In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA.JOURNAL, Collins A, Morton NE, Likelihood ratios for DNA identification, Proceedings of the National Academy of Sciences of the United States of America, 91, 13, 6007–11, June 1994, 8016106, 44126, 10.1073/pnas.91.13.6007, 1994PNAS...91.6007C, However, identification can be complicated if the scene is contaminated with DNA from several people.JOURNAL, Weir BS, Triggs CM, Starling L, Stowell LI, Walsh KA, Buckleton J, Interpreting DNA mixtures, Journal of Forensic Sciences, 42, 2, 213–22, March 1997, 9068179, DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys,JOURNAL, Jeffreys AJ, Wilson V, Thein SL, Individual-specific 'fingerprints' of human DNA, Nature, 316, 6023, 76–79, 1985, 2989708, 10.1038/316076a0, 1985Natur.316...76J, and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.weblink" title="web.archive.org/web/20061214004903weblink">Colin Pitchfork â€“ first murder conviction on DNA evidence also clears the prime suspect Forensic Science Service Accessed 23 December 2006The development of forensic science and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defense to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime.DNA profiling is also used successfully to positively identify victims of mass casualty incidents,WEB,weblink DNA Identification in Mass Fatality Incidents, September 2006, National Institute of Justice, yes,weblink" title="web.archive.org/web/20061112000837weblink">weblink 12 November 2006, bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.DNA profiling is also used in DNA paternity testing to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal DNA sequencing methods happen after birth, but there are new methods to test paternity while a mother is still pregnant."Paternity Blood Tests That Work Early in a Pregnancy" New York Times June 20, 2012 {{webarchive|url=https://web.archive.org/web/20170624231639weblink |date=24 June 2017 }}

DNA enzymes or catalytic DNA

{{further|Deoxyribozyme}}Deoxyribozymes, also called DNAzymes or catalytic DNA, were first discovered in 1994.JOURNAL, Breaker RR, Joyce GF, A DNA enzyme that cleaves RNA, Chemistry & Biology, 1, 4, 223–29, December 1994, 9383394, 10.1016/1074-5521(94)90014-0, They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, and etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction.JOURNAL, Chandra M, Sachdeva A, Silverman SK, DNA-catalyzed sequence-specific hydrolysis of DNA, Nature Chemical Biology, 5, 10, 718–20, October 2009, 19684594, 2746877, 10.1038/nchembio.201, The most extensively studied class of DNAzymes is RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific), the CA1-3 DNAzymes (copper-specific),JOURNAL, Carmi N, Shultz LA, Breaker RR, In vitro selection of self-cleaving DNAs, Chemistry & Biology, 3, 12, 1039–46, December 1996, 9000012, 10.1016/S1074-5521(96)90170-2, the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific).JOURNAL, Torabi SF, Wu P, McGhee CE, Chen L, Hwang K, Zheng N, Cheng J, Lu Y, In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing, Proceedings of the National Academy of Sciences of the United States of America, 112, 19, 5903–08, May 2015, 25918425, 4434688, 10.1073/pnas.1420361112, 2015PNAS..112.5903T, The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in cells.

Bioinformatics

{{further|Bioinformatics}}Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning, and database theory.BOOK, Baldi, Pierre, Pierre Baldi, Brunak, Soren, vanc, Bioinformatics: The Machine Learning Approach, MIT Press, 2001, 978-0-262-02506-5, 45951728, String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides.BOOK, Gusfield, Dan, Algorithms on Strings, Trees, and Sequences: Computer Science and Computational Biology, Cambridge University Press, 15 January 1997, 978-0-521-58519-4, The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function.JOURNAL, Sjölander K, Phylogenomic inference of protein molecular function: advances and challenges, Bioinformatics, 20, 2, 170–79, January 2004, 14734307, 10.1093/bioinformatics/bth021, Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally.BOOK, Mount DM, Bioinformatics: Sequence and Genome Analysis, 2nd, Cold Spring Harbor Laboratory Press, 2004, 0-87969-712-1, 55106399, Cold Spring Harbor, NY, Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

DNA nanotechnology

File:DNA nanostructures.png|thumb|upright=1.8|The DNA structure at left (schematic shown) will self-assemble into the structure visualized by atomic force microscopy at right. DNA nanotechnology is the field that seeks to design nanoscale structures using the 10.1371/journal.pbio.0020073|Strong, 2004}}.{{further|DNA nanotechnology}}DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties.JOURNAL, Rothemund PW, Folding DNA to create nanoscale shapes and patterns, Nature, 440, 7082, 297–302, March 2006, 16541064, 10.1038/nature04586, 2006Natur.440..297R, DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra.JOURNAL, Andersen ES, Dong M, Nielsen MM, Jahn K, Subramani R, Mamdouh W, Golas MM, Sander B, Stark H, Oliveira CL, Pedersen JS, Birkedal V, Besenbacher F, Gothelf KV, Kjems J, Self-assembly of a nanoscale DNA box with a controllable lid, Nature, 459, 7243, 73–76, May 2009, 19424153, 10.1038/nature07971, 2009Natur.459...73A, Nanomechanical devices and algorithmic self-assembly have also been demonstrated,JOURNAL, Ishitsuka Y, Ha T, DNA nanotechnology: a nanomachine goes live, Nature Nanotechnology, 4, 5, 281–82, May 2009, 19421208, 10.1038/nnano.2009.101, 2009NatNa...4..281I, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.JOURNAL, Aldaye FA, Palmer AL, Sleiman HF, Assembling materials with DNA as the guide, Science, 321, 5897, 1795–99, September 2008, 18818351, 10.1126/science.1154533, 2008Sci...321.1795A,

History and anthropology

{{further|Phylogenetics|Genetic genealogy}}Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny.JOURNAL, Wray GA, Dating branches on the tree of life using DNA, Genome Biology, 3, 1, REVIEWS0001, 2002, 11806830, 150454, 10.1186/gb-2001-3-1-reviews0001, true, This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology.

Information storage

DNA as a storage device for information has enormous potential since it has much higher storage density compared to electronic devices. However high costs, extremely slow read and write times (memory latency), and insufficient reliability has prevented its practical use.JOURNAL, Panda D, Molla KA, Baig MJ, Swain A, Behera D, Dash M, DNA as a digital information storage device: hope or hype?, 3 Biotech, 8, 5, 239, May 2018, 29744271, 10.1007/s13205-018-1246-7, 5935598, JOURNAL, Akram F, Haq IU, Ali H, Laghari AT, Trends to store digital data in DNA: an overview, Molecular Biology Reports, 45, 5, 1479–1490, October 2018, 30073589, 10.1007/s11033-018-4280-y,

History

{{further|History of molecular biology}}File:Maclyn McCarty with Francis Crick and James D Watson - 10.1371 journal.pbio.0030341.g001-O.jpg|thumb|James Watson and Francis CrickFrancis Crick(File:Pencil sketch of the DNA double helix by Francis Crick Wellcome L0051225.jpg|thumb|right|Pencil sketch of the DNA double helix by Francis Crick in 1953)DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".JOURNAL, Miescher, Friedrich, vanc, 1871,weblink Ueber die chemische Zusammensetzung der Eiterzellen, German, On the chemical composition of pus cells, Medicinisch-chemische Untersuchungen, 4, 441–60, Ich habe mich daher später mit meinen Versuchen an die ganzen Kerne gehalten, die Trennung der Körper, die ich einstweilen ohne weiteres Präjudiz als lösliches und unlösliches Nuclein bezeichnen will, einem günstigeren Material überlassend. (Therefore, in my experiments I subsequently limited myself to the whole nucleus, leaving to a more favorable material the separation of the substances, that for the present, without further prejudice, I will designate as soluble and insoluble nuclear material ("Nuclein"), JOURNAL, Dahm R, Discovering DNA: Friedrich Miescher and the early years of nucleic acid research, Human Genetics, 122, 6, 565–81, January 2008, 17901982, 10.1007/s00439-007-0433-0, In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases.See:
  • JOURNAL, Kossel A, 1879,weblink Ueber Nucleïn der Hefe, German, On nuclein in yeast, Zeitschrift für physiologische Chemie, 3, 284–91,
  • JOURNAL, Kossel A, 1880,weblink Ueber Nucleïn der Hefe II, German, On nuclein in yeast, Part 2, Zeitschrift für physiologische Chemie, 4, 290–95,
  • JOURNAL, Kossel A, 1881,weblink Ueber die Verbreitung des Hypoxanthins im Thier- und Pflanzenreich, German, On the distribution of hypoxanthins in the animal and plant kingdoms, Zeitschrift für physiologische Chemie, 5, 267–71,
  • BOOK, Kossel A, Untersuchungen über die Nucleine und ihre Spaltungsprodukte, German, Investigations into nuclein and its cleavage products, Strassburg, Germany, Trübne KJ, 1881, 19,
  • JOURNAL, Kossel A, 1882,weblink Ueber Xanthin und Hypoxanthin, On xanthin and hypoxanthin, Zeitschrift für physiologische Chemie, 6, 422–31,
  • Albrect Kossel (1883) "Zur Chemie des Zellkerns" {{webarchive|url=https://web.archive.org/web/20171117235430weblink |date=17 November 2017 }} (On the chemistry of the cell nucleus), Zeitschrift für physiologische Chemie, 7 : 7–22.
  • JOURNAL, Kossel A, 1886, Weitere Beiträge zur Chemie des Zellkerns, German, Further contributions to the chemistry of the cell nucleus, Zeitschrift für Physiologische Chemie, 10, 248–64,weblink On p. 264, Kossel remarked presciently: Der Erforschung der quantitativen Verhältnisse der vier stickstoffreichen Basen, der Abhängigkeit ihrer Menge von den physiologischen Zuständen der Zelle, verspricht wichtige Aufschlüsse über die elementaren physiologisch-chemischen Vorgänge. (The study of the quantitative relations of the four nitrogenous bases—[and] of the dependence of their quantity on the physiological states of the cell—promises important insights into the fundamental physiological-chemical processes.), JOURNAL, Jones ME, Albrecht Kossel, a biographical sketch, The Yale Journal of Biology and Medicine, 26, 1, 80–97, September 1953, 13103145, 2599350, National Center for Biotechnology Information,
In 1909, Phoebus Levene identified the base, sugar, and phosphate nucleotide unit of the RNA (then named "yeast nucleic acid").JOURNAL, Levene PA, Jacobs WA, 1909, Über Inosinsäure, German, Berichte der deutschen chemischen Gesellschaft, 42, 1198–203, 10.1002/cber.190904201196, JOURNAL, Levene PA, Jacobs WA, 1909, Über die Hefe-Nucleinsäure, German, Berichte der deutschen chemischen Gesellschaft, 42, 2, 2474–78, 10.1002/cber.190904202148, JOURNAL, Levene P, The structure of yeast nucleic acid, J Biol Chem, 40, 2, 415–24, 1919, In 1929, Levene identified deoxyribose sugar in "thymus nucleic acid" (DNA).JOURNAL, Cohen JS, Portugal FH, 1974, The search for the chemical structure of DNA, Connecticut Medicine, 38, 10, 551–52, 554–57,weblink Levene suggested that DNA consisted of a string of four nucleotide units linked together through the phosphate groups ("tetranucleotide hypothesis"). Levene thought the chain was short and the bases repeated in a fixed order.In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template".Koltsov proposed that a cell's genetic information was encoded in a long chain of amino acids. See:
  • SPEECH, Н. К., Кольцов, Физико-химические основы морфологии, The physical-chemical basis of morphology, Russian, 3rd All-Union Meeting of Zoologist, Anatomists, and Histologists, Leningrad, U.S.S.R., 12 December 1927,
  • Reprinted in: JOURNAL, Н. К., Кольцов, Физико-химические основы морфологии, The physical-chemical basis of morphology, Russian, Успехи экспериментальной биологии (Advances in Experimental Biology) series B, 7, 1, ?–?, 1928,
  • Reprinted in German as: JOURNAL, Nikolaj K., Koltzoff, vanc, 1928, Physikalisch-chemische Grundlagen der Morphologie, The physical-chemical basis of morphology, German, Biologisches Zentralblatt, 48, 6, 345–69,
  • In 1934, Koltsov contended that the proteins that contain a cell's genetic information replicate. See: JOURNAL, Koltzoff N, The structure of the chromosomes in the salivary glands of Drosophila, Science, 80, 2075, 312–13, October 1934, 17769043, 10.1126/science.80.2075.312, From page 313: "I think that the size of the chromosomes in the salivary glands [of Drosophila] is determined through the multiplication of genonemes. By this term I designate the axial thread of the chromosome, in which the geneticists locate the linear combination of genes; … In the normal chromosome there is usually only one genoneme; before cell-division this genoneme has become divided into two strands.", 1934Sci....80..312K, JOURNAL, Soyfer VN, The consequences of political dictatorship for Russian science, Nature Reviews Genetics, 2, 9, 723–29, September 2001, 11533721, 10.1038/35088598, In 1928, Frederick Griffith in his experiment discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form.JOURNAL, Griffith F, The Significance of Pneumococcal Types, The Journal of Hygiene, 27, 2, 113–59, January 1928, 20474956, 2167760, 10.1017/S0022172400031879, JOURNAL, Lorenz MG, Wackernagel W, Bacterial gene transfer by natural genetic transformation in the environment, Microbiological Reviews, 58, 3, 563–602, September 1994, 7968924, 372978, This system provided the first clear suggestion that DNA carries genetic information.
In 1933, while studying virgin sea urchin eggs, Jean Brachet suggested that DNA is found in the cell nucleus and that RNA is present exclusively in the cytoplasm. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH.JOURNAL, Brachet J, 1933, Recherches sur la synthese de l'acide thymonucleique pendant le developpement de l'oeuf d'Oursin, Italian, Archives de Biologie, 44, 519–76, BOOK, Burian R, 1994, Jean Brachet's Cytochemical Embryology: Connections with the Renovation of Biology in France?, Debru C, Gayon J, Picard JF, Les sciences biologiques et médicales en France 1920–1950, 2, Cahiers pour I'histoire de la recherche, Paris, CNRS Editions, 207–20,weblink In 1937, William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.See:
  • JOURNAL, Astbury WT, Bell FO, 1938, Some recent developments in the X-ray study of proteins and related structures, Cold Spring Harbor Symposia on Quantitative Biology, 6, 109–21,weblinkweblink" title="web.archive.org/web/20140714204539weblink">weblink 14 July 2014, 10.1101/sqb.1938.006.01.013,
  • JOURNAL, Astbury WT, X-ray studies of nucleic acids, Symposia of the Society for Experimental Biology, 1, 66–76, 1947, 20257017,weblinkweblink" title="web.archive.org/web/20140705132403weblink">weblink 5 July 2014,
In 1943, Oswald Avery, along with co-workers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle, supporting Griffith's suggestion (Avery–MacLeod–McCarty experiment).JOURNAL, Avery OT, Macleod CM, McCarty M, Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III, The Journal of Experimental Medicine, 79, 2, 137–58, February 1944, 19871359, 2135445, 10.1084/jem.79.2.137, DNA's role in heredity was confirmed in 1952 when Alfred Hershey and Martha Chase in the Hershey–Chase experiment showed that DNA is the genetic material of the enterobacteria phage T2.JOURNAL, Hershey AD, Chase M, Independent functions of viral protein and nucleic acid in growth of bacteriophage, The Journal of General Physiology, 36, 1, 39–56, May 1952, 12981234, 2147348, 10.1085/jgp.36.1.39, File:TheEaglePub-Cambridge-BluePlaque.jpg|thumb|left|A blue plaque outside The Eagle pubpubLate in 1951, Francis Crick started working with James Watson at the Cavendish Laboratory within the University of Cambridge. In 1953, Watson and Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. Their double-helix, molecular model of DNA was then based on one X-ray diffraction image (labeled as "Photo 51")The B-DNA X-ray pattern on the right of this linked image {{webarchive|url=https://archive.today/20120525030457weblink |date=25 May 2012 }} was obtained by Rosalind Franklin and Raymond Gosling in May 1952 at high hydration levels of DNA and it has been labeled as "Photo 51" taken by Rosalind Franklin and Raymond Gosling in May 1952, and the information that the DNA bases are paired. On 28 February 1953 Crick interrupted patrons' lunchtime at The Eagle pub in Cambridge to announce that he and Watson had "discovered the secret of life".BOOK, Regis, Ed, vanc, 2009, What Is Life?: investigating the nature of life in the age of synthetic biology, Oxford, Oxford University Press, 0-19-538341-9, 52, Months earlier, in February 1953, Linus Pauling and Robert Corey proposed a model for nucleic acids containing three intertwined chains, with the phosphates near the axis, and the bases on the outside.JOURNAL, Pauling L, Corey RB, A Proposed Structure For The Nucleic Acids, Proceedings of the National Academy of Sciences of the United States of America, 39, 2, 84–97, February 1953, 16578429, 1063734, 10.1073/pnas.39.2.84,weblink Experimental evidence supporting the Watson and Crick model was published in a series of five articles in the same issue of Nature.WEB, Nature Archives,weblink Double Helix of DNA: 50 Years,weblink" title="web.archive.org/web/20150405140401weblink">weblink 5 April 2015, yes, Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partly supported the Watson and Crick model;WEB,weblink Original X-ray diffraction image, Oregon State Library, 6 February 2011, no,weblink" title="web.archive.org/web/20090130111849weblink">weblink 30 January 2009, this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the prior two pages of Nature. In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine.WEB,weblink The Nobel Prize in Physiology or Medicine 1962, Nobelprize.org, Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.JOURNAL, Maddox B, The double helix and the 'wronged heroine', Nature, 421, 6921, 407–08, January 2003, 12540909, 10.1038/nature01399,weblink PDF, 2003Natur.421..407M, no,weblink" title="web.archive.org/web/20161017011403weblink">weblink 17 October 2016, dmy-all, In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".SPEECH, Crick, F.H.C., vanc, A Note for the RNA Tie Club, 1955, Cambridge, England,weblinkweblink" title="web.archive.org/web/20081001223217weblink">weblink yes, 1 October 2008, Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson–Stahl experiment.JOURNAL, Meselson M, Stahl FW, The Replication of DNA in Escherichia Coli, Proceedings of the National Academy of Sciences of the United States of America, 44, 7, 671–82, July 1958, 16590258, 528642, 10.1073/pnas.44.7.671, 1958PNAS...44..671M, Further work by Crick and co-workers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley, and Marshall Warren Nirenberg to decipher the genetic code.WEB,weblink The Nobel Prize in Physiology or Medicine 1968, Nobelprize.org, These findings represent the birth of molecular biology.JOURNAL, Pray L, 2008, Discovery of DNA structure and function: Watson and Crick., Nature Education, 1, 1, 100, {{clear}}

See also

{{Div col}}
  • {{annotated link|Autosome}}
  • {{annotated link|Comparison of nucleic acid simulation software}}
  • {{annotated link|Crystallography}}
  • {{annotated link|DNA-encoded chemical library}}
  • {{annotated link|DNA microarray}}
  • {{annotated link|Genetic disorder}}
  • {{annotated link|Genetic genealogy}}
  • {{annotated link|Haplotype}}
  • {{annotated link|Meiosis}}
  • {{annotated link|Nucleic acid notation}}
  • {{annotated link|Nucleic acid sequence}}
  • {{annotated link|Pangenesis}}
  • {{annotated link|Phosphoramidite}}
  • {{annotated link|Ribosomal DNA}}
  • {{annotated link|Southern blot}}
  • {{annotated link|X-ray scattering techniques}}
  • {{annotated link|Xeno nucleic acid}}
{{Div col end}}

References

Further reading

  • BOOK, Berry, Andrew, Watson, James, James Watson, vanc, DNA: the secret of life, Alfred A. Knopf, New York, 2003, 0-375-41546-7,weblink
  • BOOK, Understanding DNA: the molecule & how it works, Calladine, Chris R., Drew, Horace R., Luisi, Ben F., Travers, Andrew A., vanc, 2003, Elsevier Academic Press, Amsterdam, 0-12-155089-3,
  • BOOK, Dennis, Carina, Julie, Clayton, vanc, 50 years of DNA, Palgrave Macmillan, Basingstoke, 2003, 1-4039-1479-6,weblink
  • BOOK, Horace Freeland Judson, Judson, Horace F, vanc, 1979, The Eighth Day of Creation: Makers of the Revolution in Biology, 0-671-22540-5, 2nd, Cold Spring Harbor Laboratory Press,
  • BOOK, Olby, Robert C., Robert Olby, vanc, The path to the double helix: the discovery of DNA, Dover Publications, New York, 1994, 0-486-68117-3, , first published in October 1974 by MacMillan, with foreword by Francis Crick; the definitive DNA textbook, revised in 1994 with a 9-page postscript
  • BOOK, Micklas, David, vanc, 2003, DNA Science: A First Course, Cold Spring Harbor Press, 978-0-87969-636-8,
  • BOOK, Ridley, Matt, vanc, Matt Ridley, Francis Crick: discoverer of the genetic code, Eminent Lives, Atlas Books, Ashland, OH, 2006, 0-06-082333-X,
  • BOOK, Olby, Robert C., vanc, Francis Crick: A Biography, Cold Spring Harbor Laboratory Press, Plainview, N.Y, 2009, 0-87969-798-9,
  • BOOK, Rosenfeld, Israel, vanc, 2010, DNA: A Graphic Guide to the Molecule that Shook the World, Columbia University Press, 978-0-231-14271-7,
  • BOOK, Schultz, Mark, Zander, Cannon, vanc, 2009, The Stuff of Life: A Graphic Guide to Genetics and DNA, Hill and Wang, 0-8090-8947-5,
  • BOOK, Gunther Stent, Stent, Gunther Siegmund, Watson, James, vanc, The Double Helix: A Personal Account of the Discovery of the Structure of DNA, Norton, New York, 1980, 0-393-95075-1,
  • BOOK, Watson, James, vanc, 2004, DNA: The Secret of Life, Random House, 978-0-09-945184-6,
  • BOOK, Maurice Wilkins, Wilkins, Maurice, vanc, The third man of the double helix the autobiography of Maurice Wilkins, University Press, Cambridge, England, 2003, 0-19-860665-6,

External links

{hide}Library resources box
|onlinebooks=yes
|by=no
|lcheading= DNA
|label=DNA
{edih}{{wikiversity}}{{Commons category|DNA}}{{Spoken Wikipedia|dna.ogg|2007-02-12}} {{Genetics}}{{Gene expression}}{{Nucleic acids}}{{Featured article}}

- content above as imported from Wikipedia
- "DNA" does not exist on GetWiki (yet)
- time: 3:47am EDT - Thu, Aug 22 2019
[ this remote article is provided by Wikipedia ]
LATEST EDITS [ see all ]
GETWIKI 09 JUL 2019
Eastern Philosophy
History of Philosophy
GETWIKI 09 MAY 2016
GETWIKI 18 OCT 2015
M.R.M. Parrott
Biographies
GETWIKI 20 AUG 2014
GETWIKI 19 AUG 2014
CONNECT