期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：14
页码：5749-5754
DOI：10.1073/pnas.0812715106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：DNA lesions that block replication can be bypassed by error-prone or error-free mechanisms. Error-prone mechanisms rely on specialized translesion synthesis (TLS) DNA polymerases that directly replicate over the lesion, whereas error-free pathways use an undamaged duplex as a template for lesion bypass. In the yeast Saccharomyces cerevisiae, most mutagenic TLS of spontaneous and induced DNA damage relies on DNA polymerase {zeta} (Pol{zeta}) activity. Here, we use a distinct mutational signature produced by Pol{zeta} in a frameshift-reversion assay to examine the role of the yeast mismatch repair (MMR) system in regulating Pol{zeta}-dependent mutagenesis. Whereas MMR normally reduces mutagenesis by removing errors introduced by replicative DNA polymerases, we find that the MMR system is required for Pol{zeta}-dependent mutagenesis. In the absence of homologous recombination, however, the error-prone Pol{zeta} pathway is not affected by MMR status. These results demonstrate that MMR promotes Pol{zeta}-dependent mutagenesis by inhibiting an alternative, error-free pathway that depends on homologous recombination. Finally, in contrast to its ability to remove mistakes made by replicative DNA polymerases, we show that MMR fails to efficiently correct errors introduced by Pol{zeta}.
