• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文OA文献 >Conditional deletion of Nbs1 in murine cells reveals its role in branching repair pathways of DNA double-strand breaks
【2h】

Conditional deletion of Nbs1 in murine cells reveals its role in branching repair pathways of DNA double-strand breaks

机译：Nbs1在小鼠细胞中的条件删除揭示了其在DNA双链断裂的分支修复途径中的作用

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

NBS1 forms a complex with MRE11 and RAD50 (MRN) that is proposed to act on the upstream of two repair pathways of DNA double-strand break (DSB), homologous repair (HR) and non-homologous end joining (NHEJ). However, the function of Nbs1 in these processes has not fully been elucidated in mammals due to the lethal phenotype of cells and mice lacking Nbs1. Here, we have constructed mouse Nbs1-null embryonic fibroblasts and embryonic stem cells, through the Cre-loxP and sequential gene targeting techniques. We show that cells lacking Nbs1 display reduced HR of the single DSB in chromosomally integrated substrate, affecting both homology-directed repair (HDR) and single-stranded annealing pathways, and, surprisingly, increased NHEJ-mediated sequence deletion. Moreover, focus formation at DSBs and chromatin recruitment of the Nbs1 partners Rad50 and Mre11 as well as Rad51 and Brca1 are attenuated in these cells, whereas the NHEJ molecule Ku70 binding to chromatin is not affected. These data provide a novel insight into the function of MRN in the branching of DSB repair pathways.
机译：NBS1与MRE11和RAD50（MRN）形成复合物，该复合物被提议在DNA双链断裂（DSB），同源修复（HR）和非同源末端连接（NHEJ）的两个修复途径的上游起作用。但是，由于缺乏Nbs1的细胞和小鼠具有致命的表型，因此在哺乳动物中尚未完全阐明Nbs1在这些过程中的功能。在这里，我们通过Cre-loxP和顺序基因靶向技术构建了小鼠Nbs1-null胚胎成纤维细胞和胚胎干细胞。我们显示缺少Nbs1的细胞在染色体整合的基质中显示单个DSB的HR降低，影响同源性定向修复（HDR）和单链退火途径，并且令人惊讶地增加了NHEJ介导的序列缺失。此外，在这些细胞中，DSBs的焦点形成和Nbs1伴侣Rad50和Mre11以及Rad51和Brca1的染色质募集被减弱，而NHEJ分子Ku70与染色质的结合不受影响。这些数据提供了MRN在DSB修复途径分支中的功能的新颖见解。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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