DNA polymerases are error-prone at RecA-mediated recombination intermediates

被引:17
|
作者
Pomerantz, Richard T. [1 ]
Goodman, Myron F. [2 ]
O'Donnell, Michael E. [3 ]
机构
[1] Temple Univ, Sch Med, Fels Inst Canc Res, Dept Biochem, Philadelphia, PA 19122 USA
[2] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA
[3] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
基金
美国国家卫生研究院;
关键词
DNA replication; homologous recombination; double-strand break repair; stress-induced mutagenesis; adaptive mutagenesis; break-induced replication; STRESS-INDUCED MUTAGENESIS; BREAK-INDUCED REPLICATION; ESCHERICHIA-COLI; KINETIC MECHANISM; ADAPTIVE MUTATION; HIGH-FIDELITY; REPAIR; BACTERIA; DINB; SWITCH;
D O I
10.4161/cc.25691
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Genetic studies have suggested that Y-family translesion DNA polymerase IV (DinB) performs error-prone recombination-directed replication (RDR) under conditions of stress due to its ability to promote mutations during double-strand break (DSB) repair in growth-limited E. coli cells. In recent studies we have demonstrated that pol IV is preferentially recruited to D-loop recombination intermediates at stress-induced concentrations and is highly mutagenic during RDR in vitro. These findings verify longstanding genetic data that have implicated pol IV in promoting stress-induced mutagenesis at D-loops. In this Extra View, we demonstrate the surprising finding that A-family pol I, which normally exhibits high-fidelity DNA synthesis, is highly error-prone at D-loops like pol IV. These findings indicate that DNA polymerases are intrinsically error-prone at RecA-mediated D-loops and suggest that auxiliary factors are necessary for suppressing mutations during RDR in non-stressed proliferating cells.
引用
收藏
页码:2558 / 2563
页数:6
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