DNA polymerases are error-prone at RecA-mediated recombination intermediates |
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Authors: | Richard T Pomerantz Myron F Goodman Michael E O'Donnell |
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Institution: | 1.Fels Institute for Cancer Research; Department of Biochemistry; Temple University School of Medicine; Philadelphia, PA USA;2.Department of Biological Sciences; University of Southern California; Los Angeles, CA USA;3.The Rockefeller University; Howard Hughes Medical Institute; New York, NY USA |
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Abstract: | 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. |
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Keywords: | DNA replication homologous recombination double-strand break repair stress-induced mutagenesis adaptive mutagenesis break-induced replication |
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