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双链断裂修复过程中基因转换与断裂诱导复制之间的同源性要求及竞争

Homology Requirements and Competition between Gene Conversion and Break-Induced Replication during Double-Strand Break Repair.

作者信息

Mehta Anuja, Beach Annette, Haber James E

机构信息

Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454, USA.

Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454, USA.

出版信息

Mol Cell. 2017 Feb 2;65(3):515-526.e3. doi: 10.1016/j.molcel.2016.12.003. Epub 2017 Jan 5.

Abstract

Saccharomyces cerevisiae mating-type switching is initiated by a double-strand break (DSB) at MATa, leaving one cut end perfectly homologous to the HMLα donor, while the second end must be processed to remove a non-homologous tail before completing repair by gene conversion (GC). When homology at the matched end is ≤150 bp, efficient repair depends on the recombination enhancer, which tethers HMLα near the DSB. Thus, homology shorter than an apparent minimum efficient processing segment can be rescued by tethering the donor near the break. When homology at the second end is ≤150 bp, second-end capture becomes inefficient and repair shifts from GC to break-induced replication (BIR). But when pol32 or pif1 mutants block BIR, GC increases 3-fold, indicating that the steps blocked by these mutations are reversible. With short second-end homology, absence of the RecQ helicase Sgs1 promotes gene conversion, whereas deletion of the FANCM-related Mph1 helicase promotes BIR.

摘要

酿酒酵母的交配型转换由MATa处的双链断裂(DSB)引发,使得一个切割末端与HMLα供体完全同源,而另一端在通过基因转换(GC)完成修复之前必须经过处理以去除非同源尾巴。当匹配末端的同源性≤150 bp时,高效修复依赖于重组增强子,该增强子将HMLα拴系在DSB附近。因此,短于明显最小有效加工片段的同源性可通过将供体拴系在断裂附近来挽救。当另一端的同源性≤150 bp时,第二末端捕获变得低效,修复从GC转变为断裂诱导复制(BIR)。但是当pol32或pif1突变体阻断BIR时,GC增加3倍,表明这些突变阻断的步骤是可逆的。在第二末端同源性较短的情况下,RecQ解旋酶Sgs1的缺失促进基因转换,而FANCM相关的Mph1解旋酶的缺失促进BIR。

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本文引用的文献

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Chromosome-refolding model of mating-type switching in yeast.酵母交配型转换的染色体重折叠模型。
Proc Natl Acad Sci U S A. 2016 Nov 8;113(45):E6929-E6938. doi: 10.1073/pnas.1607103113. Epub 2016 Oct 24.
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Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):E146-54. doi: 10.1073/pnas.1523660113. Epub 2015 Dec 29.
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