Rev1 is essential for DNA damage tolerance and non-templated immunoglobulin gene mutation in a vertebrate cell line.
The majority of DNA damage-induced mutagenesis in the yeast Saccharomyces cerevisiae arises as a result of translesion replication. This process is critically dependent on the deoxycytidyl transferase Rev1p, which forms a complex with the subunits of DNA polymerase zeta, Rev3p and Rev7p. To examine the role of Rev1 in vertebrate mutagenesis and the DNA damage response, we disrupted the gene in DT40 cells. Rev1-deficient DT40 grow slowly and are sensitive to a wide range of DNA-damaging agents. Homologous recombination repair is likely to be intact as basal and damage induced sister chromatid exchange and immunoglobulin gene conversion are unaffected. How ever, the mutant cells show a markedly reduced level of non-templated immunoglobulin gene mutation, indicating a defect in translesion bypass. Furthermore, ultraviolet exposure results in marked chromosome breakage, suggesting that replication gaps created in the absence of Rev1 cannot be efficiently repaired by recombination. Thus, Rev1-dependent translesion bypass and mutagenesis is likely to be a trade-off for the ability to complete replication of a damaged template and thereby maintain genome integrity.
Simpson
Laura J
LJ
Medical Research Council Laboratory of Molecular Biology, Division of Protein & Nucleic Acid Chemistry, Hills Road, Cambridge CB2 2QH, UK.
Sale
Julian E
JE
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D004249:DNA Damage; D017931:DNA Primers; D005785:Gene Conversion; D005803:Genes, Immunoglobulin; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D009713:Nucleotidyltransferases / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D012854:Sister Chromatid Exchange; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
D017931:DNA Primers; D009153:Mutagens; D009713:Nucleotidyltransferases; D029701:Saccharomyces cerevisiae Proteins; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases