...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Functional Interaction between Poly(ADP-Ribose) Polymerase 2 (PARP-2) and TRF2: PARP Activity Negatively Regulates TRF2
【24h】

Functional Interaction between Poly(ADP-Ribose) Polymerase 2 (PARP-2) and TRF2: PARP Activity Negatively Regulates TRF2

机译：聚（ADP-核糖）聚合酶2（PARP-2）和TRF2之间的功能相互作用：PARP活性负调节TRF2

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

摘要

The DNA damage-dependent poly(ADP-ribose) polymerase-2 (PARP-2) is, together with PARP-1, an active player of the base excision repair process, thus defining its key role in genome surveillance and protection. Telomeres are specialized DNA-protein structures that protect chromosome ends from being recognized and processed as DNA strand breaks. In mammals, telomere protection depends on the T2AG3 repeat binding protein TRF2, which has been shown to remodel telomeres into large duplex loops (t-loops). In this work we show that PARP-2 physically binds to TRF2 with high affinity. The association of both proteins requires the N-terminal domain of PARP-2 and the myb domain of TRF2. Both partners colocalize at promyelocytic leukemia bodies in immortalized telomerase-negative cells. In addition, our data show that PARP activity regulates the DNA binding activity of TRF2 via both a covalent heteromodification of the dimerization domain of TRF2 and a noncovalent binding of poly(ADP-ribose) to the myb domain of TRF2. PARP-2?/? primary cells show normal telomere length as well as normal telomerase activity compared to wild-type cells but display a spontaneously increased frequency of chromosome and chromatid breaks and of ends lacking detectable T2AG3 repeats. Altogether, these results suggest a functional role of PARP-2 activity in the maintenance of telomere integrity.
机译：DNA损伤依赖性多聚（ADP-核糖）聚合酶2（PARP-2）与PARP-1一起是碱基切除修复过程的积极参与者，因此确定了其在基因组监测和保护中的关键作用。端粒是专门的DNA-蛋白质结构，可保护染色体末端不被识别和加工成DNA链断裂。在哺乳动物中，端粒保护依赖于T 2 AG 3 重复结合蛋白TRF2，TRF2已被证明可将端粒重塑为大型双链环（t环）。在这项工作中，我们表明PARP-2在物理上与TRF2具有高亲和力。两种蛋白质的结合都需要PARP-2的N末端结构域和TRF2的myb结构域。双方在永生化的端粒酶阴性细胞中共定位在早幼粒细胞白血病体上。此外，我们的数据表明，PARP活性通过TRF2二聚化结构域的共价杂合修饰和聚（ADP-核糖）与TRF2的myb结构域的非共价结合来调节TRF2的DNA结合活性。与野生型细胞相比，PARP-2 ？/？原代细胞显示正常的端粒长度和正常的端粒酶活性，但染色体和染色单体断裂的频率自发增加，并且末端缺乏可检测的T 2 AG 3 重复。总之，这些结果表明PARP-2活性在维持端粒完整性中具有功能性作用。

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