Chemical modifications
 |  |  |
| cytosine | 5-methylcytosine | 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.[38] 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.[39] Despite the biological role of 5-methylcytosine it can deaminate to leave a thymine base, methylated cytosines are therefore particularly prone to mutations.[40] Other base modifications include adenine methylation in bacteria and the glycosylation of uracil to produce the "J-base" in kinetoplastids.[41][42]
DNA damage
- Further information: Mutation
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.[44] 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.[45] It has been estimated that in each human cell, about 500 bases suffer oxidative damage per day.[46][47] 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.[48]
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.[49][50][51] Nevertheless, due to their properties of inhibiting DNA transcription and replication, they are also used in chemotherapy to inhibit rapidly-growing cancer cells.[52]
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.[53] 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.
http://en.wikipedia.org/wiki/DNA
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