...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >A DNA Damage-Regulated BRCT-Containing Protein, TopBP1, Is Required for Cell Survival
【24h】

A DNA Damage-Regulated BRCT-Containing Protein, TopBP1, Is Required for Cell Survival

机译：细胞存活需要一种DNA损伤调控的含有BRCT的蛋白TopBP1。

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

摘要

BRCA1 carboxyl-terminal (BRCT) motifs are present in a number of proteins involved in DNA repair and/or DNA damage-signaling pathways. Human DNA topoisomerase II binding protein 1 (TopBP1) contains eight BRCT motifs and shares sequence similarity with the fission yeast Rad4/Cut5 protein and the budding yeast DPB11 protein, both of which are required for DNA damage and/or replication checkpoint controls. We report here that TopBP1 is phosphorylated in response to DNA double-strand breaks and replication blocks. TopBP1 forms nuclear foci and localizes to the sites of DNA damage or the arrested replication forks. In response to DNA strand breaks, TopBP1 phosphorylation depends on the ataxia telangiectasia mutated protein (ATM) in vivo. However, ATM-dependent phosphorylation of TopBP1 does not appear to be required for focus formation following DNA damage. Instead, focus formation relies on one of the BRCT motifs, BRCT5, in TopBP1. Antisense Morpholino oligomers against TopBP1 greatly reduced TopBP1 expression in vivo. Similar to that of ataxia telangiectasia-related protein (ATR), Chk1, or Hus1, downregulation of TopBP1 leads to reduced cell survival, probably due to increased apoptosis. Taken together, the data presented here suggest that, like its putative counterparts in yeast species, TopBP1 may be involved in DNA damage and replication checkpoint controls.
机译：BRCA1羧基末端（BRCT）基序存在于许多与DNA修复和/或DNA损伤信号通路有关的蛋白质中。人类DNA拓扑异构酶II结合蛋白1（TopBP1）包含8个BRCT基序，并且与裂变酵母Rad4 / Cut5蛋白和出芽酵母DPB11蛋白具有序列相似性，这两个都是DNA损伤和/或复制检查点控制所必需的。我们在这里报告说，TopBP1被磷酸化响应DNA双链断裂和复制块。 TopBP1形成核灶，并定位于DNA损伤位点或被阻止的复制叉位。响应DNA链断裂，TopBP1磷酸化取决于体内的共济失调毛细血管扩张突变蛋白（ATM）。但是，似乎不需要DNA损伤后的焦点形成所需的TopBP1的ATM依赖性磷酸化。相反，焦点形成依赖于TopBP1中的一种BRCT主题BRCT5。针对TopBP1的反义Morpholino低聚物大大降低了TopBP1在体内的表达。与共济失调毛细血管扩张相关蛋白（ATR），Chk1或Hus1相似，TopBP1的下调导致细胞存活率降低，可能是由于凋亡增加所致。综上所述，此处提供的数据表明，TopBP1像其在酵母中的对应物一样，可能与DNA损伤和复制检查点控制有关。

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