Mito Erica, Mokhnatkin Janet V, Steele Molly C, Buettner Victoria L, Sommer Steve S, Manthey Glenn M, Bailis Adam M
Division of Molecular Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010-3000, USA.
Genetics. 2008 Aug;179(4):1795-806. doi: 10.1534/genetics.108.089821.
Defective DNA replication can result in substantial increases in the level of genome instability. In the yeast Saccharomyces cerevisiae, the pol3-t allele confers a defect in the catalytic subunit of replicative DNA polymerase delta that results in increased rates of mutagenesis, recombination, and chromosome loss, perhaps by increasing the rate of replicative polymerase failure. The translesion polymerases Pol eta, Pol zeta, and Rev1 are part of a suite of factors in yeast that can act at sites of replicative polymerase failure. While mutants defective in the translesion polymerases alone displayed few defects, loss of Rev1 was found to suppress the increased rates of spontaneous mutation, recombination, and chromosome loss observed in pol3-t mutants. These results suggest that Rev1 may be involved in facilitating mutagenic and recombinagenic responses to the failure of Pol delta. Genome stability, therefore, may reflect a dynamic relationship between primary and auxiliary DNA polymerases.
有缺陷的DNA复制会导致基因组不稳定性水平大幅增加。在酿酒酵母中,pol3-t等位基因致使复制性DNA聚合酶δ的催化亚基出现缺陷,这可能通过提高复制性聚合酶出错率,导致诱变、重组和染色体丢失率增加。跨损伤聚合酶Pol η、Pol ζ和Rev1是酵母中一组能够在复制性聚合酶出错位点发挥作用的因子。虽然仅跨损伤聚合酶缺陷的突变体几乎没有表现出缺陷,但研究发现Rev1的缺失可抑制pol3-t突变体中观察到的自发突变、重组和染色体丢失率的增加。这些结果表明,Rev1可能参与促进对Pol δ出错的诱变和重组反应。因此,基因组稳定性可能反映了主要和辅助DNA聚合酶之间的动态关系。