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The regulation of chromatid interactions prevents aberrant crossing-over during meiotic recombination.

机译:染色单体相互作用的调节防止了减数分裂重组期间的异常交叉。

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摘要

Recombination is a component of DNA metabolism and is important for the repair of damage such as double-strand breaks (DSBs). However, aberrant recombination can lead to increased mutation rates and must be regulated. BLM, a member of the conserved family of RecQ helicases, is one factor that negatively regulates recombination. In Saccharomyces cerevisiae we found that the second end of a DSB is actively engaged in strand invasion as opposed to passively awaiting annealing to the first end as presented by the canonical model for DSB repair (DSBR) in meiosis. Additionally, in mutants of Sgs1, the budding yeast RecQ ortholog, aberrant multi-chromatid DNA intermediates formed by promiscuous invasion of the second end into multiple templates are stabilized. We present a mechanism in which Sgs1 promotes disassembly of aberrant DNA intermediates, thereby decreasing crossing-over during meiosis. Mutations in either component of the Mus81-Mms4 heterodimer, an XPF-ERCC1-like endonuclease, are synthetically lethal with the sgs1 mutant in a recombination-dependent manner. We also find a subset of unresolved recombination intermediates prevent proper meiotic progression in the sgs1 mms4 double mutant. Instead of a redundancy in function with the RecQ helicase, our evidence suggests Mus81-Mms4 acts to resolve aberrant DNA intermediates that bypass Sgs1 regulation.
机译:重组是DNA代谢的组成部分,对于修复双链断裂(DSB)等损伤很重要。但是,异常重组可导致突变率增加,必须加以调节。 BLM是RecQ解旋酶保守家族的成员,是负调控重组的因素之一。在酿酒酵母中,我们发现减数分裂中DSB修复的经典模型(DSBR)提出,DSB的第二端正积极地参与链的入侵,而不是被动地等待退火至第一端。此外,在Sgs1的突变体中,通过第二末端的混杂侵入形成的多个模板中,可使出芽的酵母RecQ正向同源物稳定的异常多染色质DNA中间体得以稳定。我们提出了一种机制,其中Sgs1促进异常DNA中间体的拆卸,从而减少减数分裂过程中的交叉。 Mus81-Mms4异二聚体(一种XPF-ERCC1内切核酸酶)的任一成分中的突变,都以sgs1突变体的重组依赖性方式致死。我们还发现了一个未解决的重组中间体的子集,可防止sgs1 mms4双突变体中适当的减数分裂进程。我们的证据表明,Mus81-Mms4的作用是解决绕过Sgs1调控的异常DNA中间体,而不是RecQ解旋酶功能上的冗余。

著录项

  • 作者

    Oh, Steve Dojin.;

  • 作者单位

    University of California, Davis.;

  • 授予单位 University of California, Davis.;
  • 学科 Biology Molecular.;Biology Genetics.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 104 p.
  • 总页数 104
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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