...
  • 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 Glycine-Arginine Domain in Control of the Human MRE11 DNA Repair Protein
【24h】

A Glycine-Arginine Domain in Control of the Human MRE11 DNA Repair Protein

机译：在人类MRE11 DNA修复蛋白的控制中的甘氨酸精氨酸域。

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

摘要

Human MRE11 is a key enzyme in DNA double-strand break repair and genome stability. Human MRE11 bears a glycine-arginine-rich (GAR) motif that is conserved among multicellular eukaryotic species. We investigated how this motif influences MRE11 function. Human MRE11 alone or a complex of MRE11, RAD50, and NBS1 (MRN) was methylated in insect cells, suggesting that this modification is conserved during evolution. We demonstrate that PRMT1 interacts with MRE11 but not with the MRN complex, suggesting that MRE11 arginine methylation occurs prior to the binding of NBS1 and RAD50. Moreover, the first six methylated arginines are essential for the regulation of MRE11 DNA binding and nuclease activity. The inhibition of arginine methylation leads to a reduction in MRE11 and RAD51 focus formation on a unique double-strand break in vivo. Furthermore, the MRE11-methylated GAR domain is sufficient for its targeting to DNA damage foci and colocalization with γ-H2AX. These studies highlight an important role for the GAR domain in regulating MRE11 function at the biochemical and cellular levels during DNA double-strand break repair.
机译：人类MRE11是DNA双链断裂修复和基因组稳定性的关键酶。人MRE11具有富含甘氨酸-精氨酸（GAR）的基序，该基序在多细胞真核生物种中是保守的。我们研究了该基序如何影响MRE11功能。单独的人类MRE11或​​MRE11，RAD50和NBS1（MRN）的复合物在昆虫细胞中被甲基化，表明这种修饰在进化过程中是保守的。我们证明PRMT1与MRE11相互作用，但不与MRN复合物相互作用，这表明MRE11精氨酸甲基化发生在NBS1和RAD50结合之前。此外，前六个甲基化的精氨酸对于调节MRE11 DNA结合和核酸酶活性至关重要。精氨酸甲基化的抑制导致MRE11和RAD51在体内独特的双链断裂上的焦点形成减少。此外，MRE11甲基化的GAR结构域足以使其靶向DNA损伤灶并与γ-H2AX共定位。这些研究突出了GAR域在DNA双链断裂修复过程中在生化和细胞水平上调节MRE11功能的重要作用。

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