DNA damage-induced mutagenesis : a novel target for cancer prevention.
Tolerance to some degree of unrepaired DNA damage is crucial for cell survival-more specifically, for the sustained functionality of the DNA replication machinery-in the presence of adverse (genotoxic) conditions. At least two mechanisms ensure such tolerance: template switching and lesion bypass. Lesion bypass, whereby unrepaired damaged DNA serves as template, involves the Y family of DNA polymerases; lesion bypass can be error-free or error-prone, depending on the nucleotide incorporated during translesion synthesis. Error-prone lesion bypass constitutes a major mechanism of mutagenesis and, in eukaryotes, is primarily effected by the DNA polymerase zeta (Polzeta) pathway. A relationship between the Y family polymerases and the Polzeta pathway is thus implicated, and conforms to the two-polymerase two-step model of lesion bypass. Based on the mutagenesis hypothesis of cancer formation, DNA damage-induced mutagenesis and its underlying molecular biology offer an intriguing potential target for cancer prevention.
Graduate Center for Toxicology, University of Kentucky, Lexington 40536, USA. zwang@pop.uky.edu
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D000818:Animals; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000145:classification / Q000502:physiology; D006801:Humans; D008957:Models, Genetic; D016296:Mutagenesis / Q000235:genetics*; D009369:Neoplasms / Q000517:prevention & control*; D013698:Templates, Genetic
D004259:DNA-Directed DNA Polymerase