• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >The S-Phase Checkpoint Is Required To Respond to R-Loops Accumulated in THO Mutants
【24h】

The S-Phase Checkpoint Is Required To Respond to R-Loops Accumulated in THO Mutants

机译：需要S相检查点来响应THO突变体中累积的R循环

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Cotranscriptional R-loops are formed in yeast mutants of the THO complex, which functions at the interface between transcription and mRNA export. Despite the relevance of R-loops in transcription-associated recombination, the mechanisms by which they trigger recombination are still elusive. In order to understand how R-loops compromise genome stability, we have analyzed the genetic interaction of THO with 26 genes involved in replication, S-phase checkpoint, DNA repair, and chromatin remodeling. We found a synthetic growth defect in double null mutants of THO and S-phase checkpoint factors, such as the replication factor C- and PCNA-like complexes. Under replicative stress, R-loop-forming THO null mutants require functional S-phase checkpoint functions but not double-strand-break repair functions for survival. Furthermore, R-loop-forming hpr1Δ mutants display replication fork progression impairment at actively transcribed chromosomal regions and trigger Rad53 phosphorylation. We conclude that R-loop-mediated DNA damage activates the S-phase checkpoint, which is required for the cell survival of THO mutants under replicative stress. In light of these results, we propose a model in which R-loop-mediated recombination is explained by template switching.
机译：共转录的R环在THO复合物的酵母突变体中形成，其在转录和mRNA输出之间的界面上起作用。尽管R环在转录相关的重组中具有相关性，但它们触发重组的机制仍然难以捉摸。为了了解R环如何损害基因组稳定性，我们分析了THO与复制，S期检查点，DNA修复和染色质重塑相关的26个基因的遗传相互作用。我们在THO和S期检查点因子，如复制因子C和PCNA样复合物的双无效突变体中发现了合成生长缺陷。在复制压力下，形成R环的THO空突变体需要功能性的S期检查点功能，而不需要双链断裂修复功能才能生存。此外，形成R环的 hpr1 Δ突变体在活跃转录的染色体区域显示复制叉进展受损并触发Rad53磷酸化。我们得出结论，R环介导的DNA损伤激活了S期检查点，这是复制应激下THO突变体的细胞存活所必需的。根据这些结果，我们提出了一个模型，其中通过模板切换来解释R环介导的重组。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号