How DNA lesions are turned into mutations within cells?
Genomes of all living organisms are constantly injured by endogenous and exogenous agents that modify the chemical integrity of DNA and in turn challenge its informational content. Despite the efficient action of numerous repair systems that remove lesions in DNA in an error-free manner, some lesions, that escape these repair mechanisms, are present when DNA is being replicated. Although replicative DNA polymerases are usually unable to copy past such lesions, it was recently discovered that cells are equipped with specialized DNA polymerases that will assist the replicative polymerase during the process of Translesion Synthesis (TLS). These TLS polymerases exhibit relaxed fidelity that allows them to copy past lesions in DNA with an inherent risk of generating mutations at high frequency. We present recent aspects related to the genetics and biochemistry of TLS and highlight some of the remaining hot topics of this field.
Pagès
Vincent
V
UPR 9003 du CNRS, Cancerogenese et Mutagenese Moleculaire et Structurale, UPR Conventionnee avec l'Universite Louis Pasteur, ESBS, Blvd S. Brant, 67400 Strasbourg, France.
Fuchs
Robert P P
RP
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D004259:DNA-Directed DNA Polymerase / Q000502:physiology; D004926:Escherichia coli / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis / Q000502:physiology*; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D009713:Nucleotidyltransferases; D029701:Saccharomyces cerevisiae Proteins; D013698:Templates, Genetic; D014983:Xeroderma Pigmentosum / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000099270:Y-Family DNA Polymerases
D002273:Carcinogens; D004259:DNA-Directed DNA Polymerase; D005656:Fungal Proteins; D009153:Mutagens; D009713:Nucleotidyltransferases; D029701:Saccharomyces cerevisiae Proteins; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases