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DNA 聚合酶在 RecA 介导的重组中间体处容易出错。

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

机构信息

Fels Institute for Cancer Research, Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA, USA.

出版信息

Cell Cycle. 2013 Aug 15;12(16):2558-63. doi: 10.4161/cc.25691. Epub 2013 Jul 29.

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.

摘要

遗传研究表明,Y 家族跨损伤 DNA 聚合酶 IV(DinB)能够在生长受限的大肠杆菌细胞中促进双链断裂(DSB)修复过程中的突变,因此在应激条件下能够进行易错重组导向复制(RDR)。在最近的研究中,我们已经证明,在应激诱导浓度下,聚合酶 IV 优先招募到 D 环重组中间体,并且在体外 RDR 过程中具有高度的突变性。这些发现验证了长期以来的遗传数据,这些数据表明聚合酶 IV 参与了促进 D 环应激诱导的突变。在这个额外的视图中,我们展示了一个令人惊讶的发现,即通常表现出高保真 DNA 合成的 A 家族聚合酶 I 在 D 环上与聚合酶 IV 一样具有高度的易错性。这些发现表明,DNA 聚合酶在 RecA 介导的 D 环上固有地易错,并且表明辅助因子对于在非应激增殖细胞中的 RDR 过程中抑制突变是必要的。

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