...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Cell cycle-dependent processing of DNA lesions controls localization of Rad9 to sites of genotoxic stress.
【24h】

Cell cycle-dependent processing of DNA lesions controls localization of Rad9 to sites of genotoxic stress.

机译：DNA损伤的细胞周期依赖性处理可控制Rad9在遗传毒性应激部位的定位。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The Rad9/Rad1/Hus1 complex functions to facilitate the ATR-mediated phosphorylation of several substrates that control the checkpoint arrest induced by DNA damage. Here we show that in response to genotoxic stress induced by different types of damaging agents, Rad9 rapidly relocalized to sites of single stranded DNA, as visualized by discrete nuclear foci that co-localize with RPA. UV light-induced Rad9 foci also colocalized with TopBP1 and gamma-H2AX. Interestingly, Rad9 foci were predominately formed in G(1) and S phase after UV light, while treatment of cells with ionizing radiation (IR) resulted in accumulation of Rad9 into foci in S and G(2). Photobleaching experiments in living cells revealed that the Rad9 protein is highly mobile in undamaged cells. However, genotoxic stress induced the immobilization of a large proportion of the protein. The proportion of Rad9 immobilization was larger in S phase and the accumulation to sites of locally damaged areas induced by UV-laser irradiation was faster during DNA replication. Inactivation of nucleotide excision repair by knock down of XPA and XPC resulted in a decrease of G(1) phase cells that displayed Rad9 foci in response to UV light, whereas IR-induced Rad9 foci were not affected. In contrast, downregulation of CtIP, which promotes DSB resection, abrogated the IR-induced Rad9 foci. These findings show that due to processing of DNA lesions into a common intermediate, which occurs in a cell cycle-dependent manner, Rad9 is able to respond to different types of genotoxic stress.
机译：Rad9 / Rad1 / Hus1复合物的功能是促进几种底物的ATR介导的磷酸化，这些底物控制着DNA损伤诱导的检查点停滞。在这里，我们显示了对不同类型的破坏剂引起的遗传毒性胁迫的响应，Rad9快速重新定位到单链DNA的位点，通过与RPA共定位的离散核灶可以看到。紫外线诱导的Rad9焦点也与TopBP1和​​gamma-H2AX共定位。有趣的是，在紫外线照射后，Rad9灶主要形成于G（1）和S相，而用电离辐射（IR）处理细胞会导致Rad9积累到S和G（2）的灶中。在活细胞中进行的漂白实验表明，Rad9蛋白在未受损的细胞中具有很高的移动性。然而，遗传毒性胁迫诱导了大部分蛋白质的固定化。在S期，Rad9固定化的比例更大，并且在DNA复制过程中，UV激光辐照诱导的局部损伤区域的聚集更快。通过敲低XPA和XPC导致的核苷酸切除修复失活导致G（1）期细胞的减少，该细胞显示出对UV光的响应，而Rad9焦点不受影响。相反，CtIP的下调促进了DSB切除，废除了IR诱导的Rad9灶。这些发现表明，由于将DNA损伤加工成共同的中间体（以依赖细胞周期的方式发生），Rad9能够对不同类型的遗传毒性胁迫作出反应。

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