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DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a base missing from the backbone of DNA, or a chemically changed base such as 8-OHdG. Damage to DNA that occurs naturally can result from metabolic or hydrolytic processes. Metabolism releases compounds that damage DNA including reactive oxygen species, reactive nitrogen species, reactive carbonyl species, lipid peroxidation products and alkylating agents, among others, while hydrolysis cleaves chemical bonds in DNA.〔De Bont R, van Larebeke N. (2004) Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis 19(3):169-185. Review. PMID 15123782〕 Naturally occurring oxidative DNA damages arise at least 10,000 times per cell per day in humans and 50,000 times or more per cell per day in rats, as documented below. DNA damage is distinctly different from mutation, although both are types of error in DNA. DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of standard base pairs. DNA damage and mutation have different biological consequences. While most DNA damages can undergo DNA repair, such repair is not 100% efficient. Un-repaired DNA damages accumulate in non-replicating cells, such as cells in the brains or muscles of adult mammals and can cause aging.〔Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). Cancer and aging as consequences of un-repaired DNA damage. In: New Research on DNA Damages (Editors: Honoka Kimura and Aoi Suzuki) Nova Science Publishers, Inc., New York, Chapter 1, pp. 1-47. open access, but read only https://www.novapublishers.com/catalog/product_info.php?products_id=43247 ISBN 978-1604565812〕〔Hoeijmakers JH. (2009) DNA damage, aging, and cancer. ''N Engl J Med''. 361(15):1475-1485. Review. PMID 19812404〕〔Freitas AA, de Magalhães JP. (2011) A review and appraisal of the DNA damage theory of ageing. Mutat Res. 728(1-2):12-22. Review. PMID 21600302〕 (Also see DNA damage theory of aging.) In replicating cells, such as cells lining the colon, errors occur upon replication of past damages in the template strand of DNA or during repair of DNA damages. These errors can give rise to mutations or epigenetic alterations.〔O'Hagan HM, Mohammad HP, Baylin SB. (2008) Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island. ''PLoS Genet''. 4(8):e1000155. PMID 18704159〕 Both of these types of alteration can be replicated and passed on to subsequent cell generations. These alterations can change gene function or regulation of gene expression and possibly contribute to progression to cancer. ==DNA damages are a major problem for life== One indication that DNA damages are a major problem for life is that DNA repair processes, to cope with ubiquitously occurring DNA damages, have been found in all cellular organisms in which DNA repair has been investigated. For example, in bacteria, a regulatory network aimed at repairing DNA damages (called the SOS response in ''Escherichia coli'') has been found in many bacterial species. ''E. coli'' RecA, a key enzyme in the SOS response pathway, is the defining member of a ubiquitous class of DNA strand-exchange proteins that are essential for homologous recombination, a pathway that maintains genomic integrity by repairing broken DNA.〔Bell JC, Plank JL, Dombrowski CC, Kowalczykowski SC. (2012) Direct imaging of RecA nucleation and growth on single molecules of SSB-coated ssDNA. ''Nature'' 491(7423):274-278. . PMID 23103864〕 Genes homologous to ''RecA'' and to other central genes in the SOS response pathway are found in almost all the bacterial genomes sequenced to date, covering a large number of phyla, suggesting both an ancient origin and a widespread occurrence of recombinational repair of DNA damage.〔Erill I, Campoy S, Barbé J. (2007) Aeons of distress: an evolutionary perspective on the bacterial SOS response. FEMS Microbiol Rev. 31(6):637-656. Review. PMID 17883408〕 Eukaryotic recombinases that are homologues of RecA are also widespread in eukaryotic organisms. For example, in fission yeast and humans, RecA homologues promote duplex-duplex DNA-strand exchange needed for repair of many types of DNA lesions.〔Murayama Y, Kurokawa Y, Mayanagi K, Iwasaki H. (2008) Formation and branch migration of Holliday junctions mediated by eukaryotic recombinases. ''Nature'' 451(7181):1018-1021. PMID 18256600〕〔Holthausen JT, Wyman C, Kanaar R. (2010) Regulation of DNA strand exchange in homologous recombination. DNA Repair (Amst) 9(12):1264-1272. PMID 20971042〕 Another indication that DNA damages are a major problem for life is that cells make large investments in DNA repair processes. As pointed out by Hoeijmakers,〔 repairing just one double-strand break could require more than 10,000 ATP molecules, as used in signaling the presence of the damage, the generation of repair foci, and the formation (in humans) of the RAD51 nucleofilament (an intermediate in homologous recombinational repair). (RAD51 is a homologue of bacterial RecA.) 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「DNA damage (naturally occurring)」の詳細全文を読む スポンサード リンク
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