Dna

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For other uses, see DNA (disambiguation).

The structure of part of a DNA double helix

Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms. The main role of DNA molecules is the long-term storage of information. DNA is often compared to a set of blueprints, since it contains the instructions needed to construct other components of cells, such as proteins and RNA molecules. The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information.

Chemically, DNA is a long polymer of simple units called nucleotides, with a backbone made of sugars and phosphate groups joined by ester bonds. Attached to each sugar is one of four types of molecules called bases. It is the sequence of these four bases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA, in a process called transcription.

Within cells, DNA is organized into structures called chromosomes. These chromosomes are duplicated before cells divide, in a process called DNA replication. Eukaryotic organisms such as animals, plants, and fungi store their DNA inside the cell nucleus, while in prokaryotes such as bacteria it is found in the cell\'s cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

Contents 1 Physical and chemical properties 1.1 Major and minor grooves 1.2 Base pairing 1.3 Sense and antisense 1.4 Supercoiling 1.5 Alternative double-helical structures 1.6 Quadruplex structures 2 Chemical modifications 2.1 Base modifications 2.2 DNA damage 3 Overview of biological functions 3.1 Genes and genomes 3.2 Transcription and translation 3.3 Replication 4 Interactions with proteins 4.1 DNA-binding proteins 4.2 DNA-modifying enzymes 4.2.1 Nucleases and ligases 4.2.2 Topoisomerases and helicases 4.2.3 Polymerases 5 Genetic recombination 6 Evolution of DNA metabolism 7 Uses in technology 7.1 Genetic engineering 7.2 Forensics 7.3 Bioinformatics 7.4 DNA nanotechnology 7.5 History and anthropology 8 History 9 See also 10 References 11 Further reading 12 External links

Physical and chemical properties

The chemical structure of DNA. Hydrogen bonds are shown as dotted lines.

DNA is a long polymer made from repeating units called nucleotides.Alberts, Bruce; Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walters (2002). Molecular Biology of the Cell; Fourth Edition. New York and London: Garland Science. ISBN 0-8153-3218-1. Butler, John M. (2001) Forensic DNA Typing "Elsevier". pp. 14–15. ISBN 978-0-12-147951-0. The DNA chain is 22 to 26 Ångströms wide (2.2 to 2.6 nanometres), and one nucleotide unit is 3.3 Å (0.33 nm) long.Mandelkern M, Elias J, Eden D, Crothers D (1981). "The dimensions of DNA in solution". J Mol Biol 152 (1): 153–61. PMID 7338906.  Although each individual repeating unit is very small, DNA polymers can be enormous molecules containing millions of nucleotides. For instance, the largest human chromosome, chromosome number 1, is approximately 220 million base pairs long.Gregory S, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature 441 (7091): 315–21. PMID 16710414. 

In living organisms, DNA does not usually exist as a single molecule, but instead as a tightly-associated pair of molecules.Watson J, Crick F (1953). "Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid". Nature 171 (4356): 737–8. PMID 13054692. Berg J., Tymoczko J. and Stryer L. (2002) Biochemistry. W. H. Freeman and Company ISBN 0-7167-4955-6 These two long strands entwine like vines, in the shape of a double helix. The nucleotide repeats contain both the segment of the backbone of the molecule, which holds the chain together, and a base, which interacts with the other DNA strand in the helix. In general, a base linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. If multiple nucleotides are linked together, as in DNA, this polymer is called a polynucleotide.Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents IUPAC-IUB Commission on Biochemical Nomenclature (CBN), Accessed 03 Jan 2006

The backbone of the DNA strand is made from alternating phosphate and sugar residues.Ghosh A, Bansal M (2003). "A glossary of DNA structures from A to Z". Acta Crystallogr D Biol Crystallogr 59 (Pt 4): 620–6. PMID 12657780.  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 asymmetric bonds mean a strand of DNA has a direction. In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand. This arrangement of DNA strands is called antiparallel. The asymmetric ends of DNA strands are referred to as the 5′ (five prime) and 3′ (three prime) ends. One of the major differences between DNA and RNA is the sugar, with 2-deoxyribose being replaced by the alternative pentose sugar ribose in RNA.

The DNA double helix is stabilized by hydrogen bonds between the bases attached to the two strands. The four bases found in DNA are adenine (abbreviated 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.

These bases are classified into two types; adenine and guanine are fused five- and six-membered heterocyclic compounds called purines, while cytosine and thymine are six-membered rings called pyrimidines. A fifth pyrimidine base, called uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine.

Major and minor grooves

Animation of the structure of a section of DNA. The bases lie horizontally between the two spiraling strands. Large versionCreated from PDB 1D65

The double helix is a right-handed spiral. As the DNA strands wind around each other, they leave gaps between each set of phosphate backbones, revealing the sides of the bases inside (see animation). There are two of these grooves twisting around the surface of the double helix: one groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide.Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, Dickerson R (1980). "Crystal structure analysis of a complete turn of B-DNA". Nature 287 (5784): 755–8. PMID 7432492.  The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove.Pabo C, Sauer R (1984). "Protein-DNA recognition". Annu Rev Biochem 53: 293–321. PMID 6236744. 

Base pairing

Further information: Base pair

Each type of base on one strand forms a bond with just one type of base on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with A bonding only to T, and C bonding only to G. This arrangement of two nucleotides binding together across the double helix is called a base pair. The double helix is also stabilized by the hydrophobic effect and pi stacking, which are not influenced by the sequence of the DNA.Ponnuswamy P, Gromiha M (1994). "On the conformational stability of oligonucleotide duplexes and tRNA molecules". J Theor Biol 169 (4): 419–32. PMID 7526075.  As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature.Clausen-Schaumann H, Rief M, Tolksdorf C, Gaub H (2000). "Mechanical stability of single DNA molecules". Biophys J 78 (4): 1997–2007. PMID 10733978.  As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.

Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Hydrogen bonds 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, left). The GC base pair is therefore stronger than the AT base pair. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine 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.Chalikian T, Völker J, Plum G, Breslauer K (1999). "A more unified picture for the thermodynamics of nucleic acid duplex melting: a characterization by calorimetric and volumetric techniques". Proc Natl Acad Sci U S A 96 (14): 7853–8. PMID 10393911.  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.deHaseth P, Helmann J (1995). "Open complex formation by Escherichia coli RNA polymerase: the mechanism of polymerase-induced strand separation of double helical DNA". Mol Microbiol 16 (5): 817–24. PMID 7476180.  In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their melting temperature (also called T_m 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.Isaksson J, Acharya S, Barman J, Cheruku P, Chattopadhyaya J (2004). "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. PMID 15609994. 

Sense and antisense

Further information: Sense (molecular biology)

A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein. 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 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.Hüttenhofer A, Schattner P, Polacek N (2005). "Non-coding RNAs: hope or hype?". Trends Genet 21 (5): 289–97. PMID 15851066.  One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.Munroe S (2004). "Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns". J Cell Biochem 93 (4): 664–71. PMID 15389973. 

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction made above between sense and antisense strands by having overlapping genes.Makalowska I, Lin C, Makalowski W (2005). "Overlapping genes in vertebrate genomes". Comput Biol Chem 29 (1): 1–12. PMID 15680581.  In these cases, some DNA sequences do double duty, encoding one protein when read 5′ to 3′ along one strand, and a second protein when read in the opposite direction (still 5′ to 3′) along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription,Johnson Z, Chisholm S (2004). "Properties of overlapping genes are conserved across microbial genomes". Genome Res 14 (11): 2268–72. PMID 15520290.  while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.Lamb R, Horvath C (1991). "Diversity of coding strategies in influenza viruses". Trends Genet 7 (8): 261–6. PMID 1771674. 

Supercoiling

Further information: 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.Benham C, Mielke S (2005). "DNA mechanics". Annu Rev Biomed Eng 7: 21–53. PMID 16004565.  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.Champoux J (2001). "DNA topoisomerases: structure, function, and mechanism". Annu Rev Biochem 70: 369–413. PMID 11395412.  These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.Wang J (2002). "Cellular roles of DNA topoisomerases: a molecular perspective". Nat Rev Mol Cell Biol 3 (6): 430–40. PMID 12042765. 

From left to right, the structures of A, B and Z DNA

Alternative double-helical structures

Further information: Mechanical properties of DNA

DNA exists in many possible conformations. However, only A-DNA, B-DNA, and Z-DNA have been observed in organisms. Which conformation DNA adopts depends on the sequence of the DNA, the amount and direction of supercoiling, chemical modifications of the bases and also solution conditions, such as the concentration of metal ions and polyamines.Basu H, Feuerstein B, Zarling D, Shafer R, Marton L (1988). "Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies". J Biomol Struct Dyn 6 (2): 299–309. PMID 2482766.  Of these three conformations, the "B" form described above is most common under the conditions found in cells.Leslie AG, Arnott S, Chandrasekaran R, Ratliff RL (1980). "Polymorphism of DNA double helices". J. Mol. Biol. 143 (1): 49–72. PMID 7441761.  The two alternative double-helical forms of DNA differ in their geometry and dimensions.

The A 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 dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes.Wahl M, Sundaralingam M (1997). "Crystal structures of A-DNA duplexes". Biopolymers 44 (1): 45–63. PMID 9097733. Lu XJ, Shakked Z, Olson WK (2000). "A-form conformational motifs in ligand-bound DNA structures". J. Mol. Biol. 300 (4): 819-40. PMID 10891271.  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.Rothenburg S, Koch-Nolte F, Haag F. "DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles". Immunol Rev 184: 286–98. PMID 12086319.  These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.Oh D, Kim Y, Rich A (2002). "Z-DNA-binding proteins can act as potent effectors of gene expression in vivo". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16666-71. PMID 12486233. 

Structure of a DNA quadruplex formed by telomere repeats. The conformation of the DNA backbone diverges significantly from the typical helical structureCreated from NDB UD0017

Quadruplex structures

Further information: 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.Greider C, Blackburn E (1985). "Identification of a specific telomere terminal transferase activity in Tetrahymena extracts". Cell 43 (2 Pt 1): 405–13. PMID 3907856.  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.Nugent C, Lundblad V (1998). "The telomerase reverse transcriptase: components and regulation". Genes Dev 12 (8): 1073–85. PMID 9553037.  In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.Wright W, Tesmer V, Huffman K, Levene S, Shay J (1997). "Normal human chromosomes have long G-rich telomeric overhangs at one end". Genes Dev 11 (21): 2801–9. PMID 9353250. 

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.Burge S, Parkinson G, Hazel P, Todd A, Neidle S (2006). "Quadruplex DNA: sequence, topology and structure". Nucleic Acids Res 34 (19): 5402–15. PMID 17012276.  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.Parkinson G, Lee M, Neidle S (2002). "Crystal structure of parallel quadruplexes from human telomeric DNA". Nature 417 (6891): 876–80. PMID 12050675.  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.Griffith J, Comeau L, Rosenfield S, Stansel R, Bianchi A, Moss H, de Lange T (1999). "Mammalian telomeres end in a large duplex loop". Cell 97 (4): 503–14. PMID 10338214.  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.

Chemical modifications

cytosine	5-methylcytosine	thymine

Structure of cytosine with and without the 5-methyl group. After deamination the 5-methylcytosine has the same structure as thymine

Base modifications

Further information: DNA methylation

The expression of genes is influenced by the chromatin structure of a chromosome and regions of that have low or no gene expression usually contain high levels of methylation of cytosine bases. For example, cytosine methylation, producing 5-methylcytosine, is important for X-chromosome inactivation.Klose R, Bird A (2006). "Genomic DNA methylation: the mark and its mediators". Trends Biochem Sci 31 (2): 89–97. PMID 16403636.  The average level of methylation varies between organisms, with Caenorhabditis elegans lacking cytosine methylation, while vertebrates show higher levels, with up to 1% of their DNA containing 5-methylcytosine.Bird A (2002). "DNA methylation patterns and epigenetic memory". Genes Dev 16 (1): 6–21. PMID 11782440.  Despite the biological role of 5-methylcytosine it can deaminate to leave a thymine base, methylated cytosines are therefore particularly prone to mutations.Walsh C, Xu G. "Cytosine methylation and DNA repair". Curr Top Microbiol Immunol 301: 283–315. PMID 16570853.  Other base modifications include adenine methylation in bacteria and the glycosylation of uracil to produce the "J-base" in kinetoplastids.Ratel D, Ravanat J, Berger F, Wion D (2006). "N6-methyladenine: the other methylated base of DNA". Bioessays 28 (3): 309–15. PMID 16479578. Gommers-Ampt J, Van Leeuwen F, de Beer A, Vliegenthart J, Dizdaroglu M, Kowalak J, Crain P, Borst P (1993). "beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei". Cell 75 (6): 1129–36. PMID 8261512. 

DNA damage

Further information: Mutation

Benzopyrene, the major mutagen in tobacco smoke, in an adduct to DNACreated from PDB 1JDG

DNA can be damaged by many different sorts of mutagens, which are agents that change the DNA sequence. These agents 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 mostly damages DNA by producing thymine dimers, which are cross-links between adjacent pyrimidine bases in a DNA strand.Douki T, Reynaud-Angelin A, Cadet J, Sage E (2003). "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): 9221–6. PMID 12885257. , On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, as well as double-strand breaks.Cadet J, Delatour T, Douki T, Gasparutto D, Pouget J, Ravanat J, Sauvaigo S (1999). "Hydroxyl radicals and DNA base damage". Mutat Res 424 (1–2): 9–21. PMID 10064846.  It has been estimated that in each human cell, about 500 bases suffer oxidative damage per day.Shigenaga M, Gimeno C, Ames B (1989). "Urinary 8-hydroxy-2′-deoxyguanosine as a biological marker of in vivo oxidative DNA damage". Proc Natl Acad Sci U S A 86 (24): 9697–701. PMID 2602371. Cathcart R, Schwiers E, Saul R, Ames B (1984). "Thymine glycol and thymidine glycol in human and rat urine: a possible assay for oxidative DNA damage". Proc Natl Acad Sci U S A 81 (18): 5633–7. PMID 6592579.  Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions and deletions from the DNA sequence, as well as chromosomal translocations.Valerie K, Povirk L (2003). "Regulation and mechanisms of mammalian double-strand break repair". Oncogene 22 (37): 5792–812. PMID 12947387. 

Many mutagens intercalate into the space between two adjacent base pairs. Intercalators are mostly aromatic and planar molecules, and include ethidium, daunomycin, doxorubicin and thalidomide. In order for an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. These structural changes inhibit both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators are often carcinogens, with benzopyrene diol epoxide, acridines, aflatoxin and ethidium bromide being well-known examples.Ferguson L, Denny W (1991). "The genetic toxicology of acridines". Mutat Res 258 (2): 123–60. PMID 1881402. Jeffrey A (1985). "DNA modification by chemical carcinogens". Pharmacol Ther 28 (2): 237–72. PMID 3936066. Stephens T, Bunde C, Fillmore B (2000). "Mechanism of action in thalidomide teratogenesis". Biochem Pharmacol 59 (12): 1489–99. PMID 10799645.  Nevertheless, due to their properties of inhibiting DNA transcription and replication, they are also used in chemotherapy to inhibit rapidly-growing cancer cells.Braña M, Cacho M, Gradillas A, de Pascual-Teresa B, Ramos A (2001). "Intercalators as anticancer drugs". Curr Pharm Des 7 (17): 1745–80. PMID 11562309. 

Overview of biological functions

DNA 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.Venter J, et al. (2001). "The sequence of the human genome". Science 291 (5507): 1304–51. PMID 11181995.  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. Alternatively, 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 we focus on the interactions between DNA and other molecules that mediate the function of the genome.

Genes and genomes

Further information: Cell nucleus, Chromatin, Chromosome, Gene, Noncoding DNA

Genomic DNA is located in the cell nucleus of eukaryotes, as well as small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid.Thanbichler M, Wang S, Shapiro L (2005). "The bacterial nucleoid: a highly organized and dynamic structure". J Cell Biochem 96 (3): 506–21. PMID 15988757.  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, as well as regulatory sequences such as promoters and enhancers, which control the 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.Wolfsberg T, McEntyre J, Schuler G (2001). "Guide to the draft human genome". Nature 409 (6822): 824–6. PMID 11236998.  The reasons for the presence of so much non-coding 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."Gregory T (2005). "The C-value enigma in plants and animals: a review of parallels and an appeal for partnership". Ann Bot (Lond) 95 (1): 133–46. PMID 15596463.  However, DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.The ENCODE Project Consortium (2007). "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project". Nature 447 (7146): 799-816. doi:doi:10.1038/nature05874. 

T7 RNA polymerase (blue) producing a mRNA (green) from a DNA template (orange).Created from PDB 1MSW

Some non-coding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes, but are important for the function and stability of chromosomes.Pidoux A, Allshire R (2005). "The role of heterochromatin in centromere function". Philos Trans R Soc Lond B Biol Sci 360 (1455): 569–79. PMID 15905142.  An abundant form of non-coding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation.Harrison P, Hegyi H, Balasubramanian S, Luscombe N, Bertone P, Echols N, Johnson T, Gerstein M (2002). "Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22". Genome Res 12 (2): 272–80. PMID 11827946.  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.Harrison P, Gerstein M (2002). "Studying genomes through the aeons: protein families, pseudogenes and proteome evolution". J Mol Biol 318 (5): 1155–74. PMID 12083509. 

Transcription and translation

Further information: 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 ($4^3$ 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.

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 ligase joins them together.

Replication

Further information: 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.Albà M (2001). "Replicative DNA polymerases". Genome Biol 2 (1): REVIEWS3002. PMID 11178285.  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.

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

Interaction of DNA with histones (shown in white, top). These proteins\' basic amino acids (below left, blue) bind to the acidic phosphate groups on DNA (below right, red).

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.Sandman K, Pereira S, Reeve J (1998). "Diversity of prokaryotic chromosomal proteins and the origin of the nucleosome". Cell Mol Life Sci 54 (12): 1350–64. PMID 9893710. Dame RT (2005). "The role of nucleoid-associated proteins in the organization and compaction of bacterial chromatin". Mol. Microbiol. 56 (4): 858-70. PMID 15853876.  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 therefore largely independent of the base sequence.Luger K, Mäder A, Richmond R, Sargent D, Richmond T (1997). "Crystal structure of the nucleosome core particle at 2.8 A resolution". Nature 389 (6648): 251–60. PMID 9305837.  Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation.Jenuwein T, Allis C (2001). "Translating the histone code". Science 293 (5532): 1074–80. PMID 11498575.  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.Ito T. "Nucleosome assembly and remodelling". Curr Top Microbiol Immunol 274: 1–22. PMID 12596902.  Other non-specific DNA-binding proteins found in chromatin include the high-mobility group proteins, which bind preferentially to bent or distorted DNA.Thomas J (2001). "HMG1 and 2: architectural DNA-binding proteins". Biochem Soc Trans 29 (Pt 4): 395–401. PMID 11497996.  These proteins are important in bending arrays of nucleosomes and arranging them into more complex chromatin structures.Grosschedl R, Giese K, Pagel J (1994). "HMG domain proteins: architectural elements in the assembly of nucleoprotein structures". Trends Genet 10 (3): 94–100. PMID 8178371. 

A distinct group of DNA-binding proteins are the single-stranded-DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-characterised member of this family and is essential for most processes where the double helix is separated, including DNA replication, recombination and DNA repair.Iftode C, Daniely Y, Borowiec J (1999). "Replication protein A (RPA): the eukaryotic SSB". Crit Rev Biochem Mol Biol 34 (3): 141–80. PMID 10473346.  These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

The lambda repressor helix-turn-helix transcription factor bound to its DNA targetCreated from PDB 1LMB

In contrast, other proteins have evolved to specifically bind particular DNA sequences. The most intensively studied of these are the various classes of transcription factors, which are proteins that regulate transcription. Each one of these proteins bind to one particular set of DNA sequences a