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首页> 外文期刊>Cell cycle >Roles of DNA helicases and Exo1 in the avoidance of mutations induced by Top1-mediated cleavage at ribonucleotides in DNA
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Roles of DNA helicases and Exo1 in the avoidance of mutations induced by Top1-mediated cleavage at ribonucleotides in DNA

机译:DNA解旋酶和Exo1在避免由Top1介导的DNA核糖核苷酸裂解引起的突变中的作用

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摘要

The replicative DNA polymerases insert ribonucleotides into DNA at a frequency of approximately 1/6500 nucleotides replicated. The rNMP residues make the DNA backbone more susceptible to hydrolysis and can also distort the helix, impeding the transcription and replication machineries. rNMPs in DNA are efficiently removed by RNaseH2 by a process called ribonucleotides excision repair (RER). In the absence of functional RNaseH2, rNMPs are subject to cleavage by Topoisomerase I, followed by further processing to result in deletion mutations due to slippage in simple DNA repeats. The topoisomerase I-mediated cleavage at rNMPs results in DNA ends that cannot be ligated by DNA ligase I, a 5 ' OH end and a 2 '-3 ' cyclic phosphate end. In the budding yeast, the mutation level in RNaseH2 deficient cells is kept low via the action of the Srs2 helicase and the Exo1 nuclease, which collaborate to process the Top1-induced nick with subsequent non-mutagenic gap filling. We have surveyed other helicases and nucleases for a possible role in reducing mutagenesis at Top1 nicks at rNMPs and have uncovered a novel role for the RecQ family helicase Sgs1 in this process.
机译:复制性DNA聚合酶以大约1/6500个核苷酸的复制频率将核糖核苷酸插入DNA。 rNMP残基使DNA主链更易于水解,并且还会扭曲螺旋,从而阻碍转录和复制机制。 RNaseH2通过称为核糖核苷酸切除修复(RER)的过程有效去除了DNA中的rNMP。在不存在功能性RNaseH2的情况下,rNMP会被拓扑异构酶I切割,然后进行进一步处理,由于简单DNA重复序列的滑动而导致缺失突变。拓扑异构酶I介导的rNMP裂解导致DNA末端无法被DNA连接酶I连接,即5'OH末端和2'-3'环状磷酸酯末端。在出芽的酵母中,通过Srs2解旋酶和Exo1核酸酶的作用将RNaseH2缺陷细胞中的突变水平保持在较低水平,这两个酶共同处理Top1诱导的缺口,并随后进行非诱变的缺口填充。我们已经调查了其他解旋酶和核酸酶在减少rNMP上Top1切口诱变中的可能作用,并在此过程中发现了RecQ家族解旋酶Sgs1的新作用。

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