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Mutation
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=== Spontaneous mutation === ''Spontaneous mutations'' occur with non-zero probability even given a healthy, uncontaminated cell. Naturally occurring oxidative DNA damage is estimated to occur 10,000 times per cell per day in humans and 100,000 times per cell per day in [[rat]]s.<ref>{{cite journal | vauthors = Ames BN, Shigenaga MK, Hagen TM | title = Oxidants, antioxidants, and the degenerative diseases of aging | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 17 | pages = 7915β22 | date = September 1993 | pmid = 8367443 | pmc = 47258 | doi = 10.1073/pnas.90.17.7915 | bibcode = 1993PNAS...90.7915A | doi-access = free }}</ref> Spontaneous mutations can be characterized by the specific change:<ref>{{cite web |url=http://www-personal.ksu.edu/~bethmont/mutdes.html#origins |title=Mutation, Mutagens, and DNA Repair | vauthors = Montelone BA |year=1998 |website=www-personal.ksu.edu |access-date=2 October 2015 |url-status=dead |archive-url=https://web.archive.org/web/20150926115801/http://www-personal.ksu.edu/~bethmont/mutdes.html#origins |archive-date=26 September 2015 }}</ref> * [[Tautomer]]ism β A base is changed by the repositioning of a [[hydrogen]] atom, altering the hydrogen bonding pattern of that base, resulting in incorrect [[base pair]]ing during replication.<ref>{{cite journal | vauthors = Slocombe L, Al-Khalili JS, Sacchi M | title = Quantum and classical effects in DNA point mutations: Watson-Crick tautomerism in AT and GC base pairs | journal = Physical Chemistry Chemical Physics | volume = 23 | issue = 7 | pages = 4141β4150 | date = February 2021 | pmid = 33533770 | doi = 10.1039/D0CP05781A| issn=1463-9076 | bibcode = 2021PCCP...23.4141S | s2cid = 231788542 | doi-access = free }}</ref> Theoretical results suggest that [[proton tunnelling]] is an important factor in the spontaneous creation of GC [[tautomer]]s.<ref>{{Cite journal | vauthors = Slocombe L, Sacchi M, Al-Khalili J |date=5 May 2022 |title=An open quantum systems approach to proton tunnelling in DNA |url=https://www.nature.com/articles/s42005-022-00881-8 |journal=Communications Physics |language=en |volume=5 |issue=1 |page=109 |doi=10.1038/s42005-022-00881-8 |arxiv=2110.00113 |bibcode=2022CmPhy...5..109S |s2cid=238253421 |issn=2399-3650}}</ref> * [[Depurination]] β Loss of a [[purine]] base (A or G) to form an apurinic site ([[AP site]]). * [[Deamination]] β [[Hydrolysis]] changes a normal base to an atypical base containing a [[Ketone|keto]] group in place of the original [[amine]] group. Examples include C β U and A β HX ([[hypoxanthine]]), which can be corrected by DNA repair mechanisms; and 5MeC ([[5-methylcytosine]]) β T, which is less likely to be detected as a mutation because [[thymine]] is a normal DNA base. * [[Slipped strand mispairing]] β Denaturation of the new strand from the template during replication, followed by renaturation in a different spot ("slipping"). This can lead to insertions or deletions.
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