Y-family DNA polymerases in mammalian cells.
Eukaryotic genomes are replicated with high fidelity to assure the faithful transmission of genetic information from one generation to the next. The accuracy of replication relies heavily on the ability of replicative DNA polymerases to efficiently select correct nucleotides for the polymerization reaction and, using their intrinsic exonuclease activities, to excise mistakenly incorporated nucleotides. Cells also possess a variety of specialized DNA polymerases that, by a process called translesion DNA synthesis (TLS), help overcome replication blocks when unrepaired DNA lesions stall the replication machinery. This review considers the properties of the Y-family (a subset of specialized DNA polymerases) and their roles in modulating spontaneous and genotoxic-induced mutations in mammals. We also review recent insights into the molecular mechanisms that regulate PCNA monoubiquitination and DNA polymerase switching during TLS and discuss the potential of using Y-family DNA polymerases as novel targets for cancer prevention and therapy.
Guo
Caixia
C
Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9072, USA. caixia.guo@utsouthwestern.edu
Kosarek-Stancel
J Nicole
JN
Tang
Tie-Shan
TS
Friedberg
Errol C
EC
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000145:classification* / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D006801:Humans; D016296:Mutagenesis; D009153:Mutagens; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics
D009153:Mutagens; D018809:Proliferating Cell Nuclear Antigen; D004259:DNA-Directed DNA Polymerase