Editing Mutagenesis (section)

=== DNA damage and spontaneous mutation ===
The number of [[DNA damage (naturally occurring)|DNA damage]] episodes occurring in a mammalian cell per day is high (more than 60,000 per day). Frequent occurrence of DNA damage is likely a problem for all DNA- containing organisms, and the need to cope with DNA damage and minimize their deleterious effects is likely a fundamental problem for life.{{Citation needed|date=December 2019|reason=removed citation to predatory publisher content}}

Most spontaneous mutations likely arise from [[DNA repair#Translesion synthesis|error-prone trans-lesion synthesis]] past a DNA damage site in the template strand during DNA replication. This process can overcome potentially lethal blockages, but at the cost of introducing inaccuracies in daughter DNA. The causal relationship of DNA damage to spontaneous mutation is illustrated by aerobically growing ''E. coli'' bacteria, in which 89% of spontaneously occurring base substitution mutations are caused by reactive oxygen species (ROS)-induced DNA damage.<ref>{{cite journal|vauthors=Sakai A, Nakanishi M, Yoshiyama K, Maki H|date=July 2006|title=Impact of reactive oxygen species on spontaneous mutagenesis in ''Escherichia coli''|journal=Genes Cells|volume=11|issue=7|pages=767–78|doi=10.1111/j.1365-2443.2006.00982.x|pmid=16824196|s2cid=1365658|doi-access=free}}</ref> In yeast, more than 60% of spontaneous single-base pair substitutions and deletions are likely caused by trans-lesion synthesis.<ref>{{cite journal|vauthors=Kunz BA, Ramachandran K, Vonarx EJ|date=April 1998|title=DNA sequence analysis of spontaneous mutagenesis in ''Saccharomyces cerevisiae''|url=http://www.genetics.org/cgi/pmidlookup?view=long&pmid=9560369|journal=Genetics|volume=148|issue=4|pages=1491–505|doi=10.1093/genetics/148.4.1491|pmc=1460101|pmid=9560369}}</ref>

An additional significant source of mutations in eukaryotes is the inaccurate DNA repair process [[non-homologous end joining]], that is often employed in repair of double strand breaks.<ref>{{cite journal|author=Huertas P|date=January 2010|title=DNA resection in eukaryotes: deciding how to fix the break|journal=Nat. Struct. Mol. Biol.|volume=17|issue=1|pages=11–6|doi=10.1038/nsmb.1710|pmc=2850169|pmid=20051983}}</ref>

In general, it appears that the main underlying cause of spontaneous mutation is error-prone trans-lesion synthesis during DNA replication and that the error-prone non-homologous end-joining repair pathway may also be an important contributor in eukaryotes.