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favicon.ico: en.wikipedia.org/wiki/DNA - DNA - Wikipedia.

site address: en.wikipedia.org/wiki/DNA

site title: DNA - Wikipedia

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dna, and, modifications, packaging, proteins, genetic, history, bases, base, alternative, structures, enzymes, contents, properties, chemical, altered, biological, functions, interactions, with, recombination, evolution, uses, in, technology, see, also, references, further, reading, external, links, nucleobase, classification, non, canonical, grooves, pairing, amount, sense, antisense, supercoiling, chemistry, quadruplex, branched, artificial, acidity, macroscopic, appearance, damage, genomes, transcription, translation, replication, extracellular, nucleic, acids, binding, modifying, engineering, profiling, or, catalytic, bioinformatics, nanotechnology, anthropology, information, storage, ssdna, vs, dsdna, nucleases, ligases, topoisomerases, helicases, polymerases,

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ons include adenine methylation in bacteria the presence of 5 hydroxymethylcytosine in the brain 79 and the glycosylation of uracil to produce the j base in kinetoplastids 80 81 damage further information dna damage naturally occurring mutation and dna damage theory of aging a covalent adduct between a metabolically activated form of benzo a pyrene the major mutagen in tobacco smoke and dna 82 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 83 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 84 a typical human cell contains about 150 000 bases that have suffered oxidative damage 85 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 86 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 87 88 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 89 90 91 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 92 as a result dna intercalators may be carcinogens and in the case of thalidomide a teratogen 93 others such as benzo a pyrene diol epoxide and aflatoxin form dna adducts that induce errors in replication 94 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 95 biological functions location of eukaryote nuclear dna within the chromosomes 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 96 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 an alternative fashion a cell may 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 genomes 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 97 the functional genetic information in a genome is located in genes regulatory sequences origins of replication centromeres telomeres and segments required for the three dimensional structure of chromatin in many complex eukaryotes only a small fraction of the total sequence is devoted to the various functional elements for example in humans less than 10 of the genome has a defined functional role and the rest 90 is probably junk dna see also non coding dna transcription and translation further information genetic code transcription genetics and 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 tag taa and tga codons uag uaa and uga on the mrna replication further information dna replication dna replication the double helix is unwound by a helicase and topo iso merase 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 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 98 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 99 various possible functions have been proposed for edna it may be involved in horizontal gene transfer 100 it may provide nutrients 101 and it may act as a buffer to recruit or titrate ions or antibiotics 102 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 103 it may contribute to biofilm formation 104 and it may contribute to the biofilm s physical strength and resistance to biological stress 105 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 106 under the name of environmental dna edna has seen increased use in the natural sciences as a survey tool for ecology monitoring the movements and presence of species in water air or on land and assessing an area s biodiversity 107 108 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 information dna binding protein 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 109 110 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 111 chemical modifications of these basic amino acid residues include methylation phosphorylation and acetylation 112 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 113 other non specific dna binding proteins in chromatin include the high mobility group proteins which bind to bent or distorted dna 114 these proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes 115 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 116 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 target 117 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 118 alternatively transcription factors can bind enzymes that modify the histones at the promoter this changes the accessibility of the dna template to the polymerase 119 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 120 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 25 dna modifying enzymes nucleases and ligases the restriction enzyme ecorv green in a complex with its substrate dna 121 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 122 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 123 ligases are particularly important in lagging strand dna replication as they join 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 123 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 44 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 124 topoisomerases are required for many processes involving dna such as dna replication and transcription 45 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 125 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 126 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 mak...
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