• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Active and Passive Destabilization of G-Quadruplex DNA by the Telomere POT1-TPP1 Complex
【24h】

Active and Passive Destabilization of G-Quadruplex DNA by the Telomere POT1-TPP1 Complex

机译：通过Telomete Pot1-TPP1复合物激活和被动稳定的G-Quadreplex DNA

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

Chromosome ends are protected by guanosine-rich telomere DNA that forms stable G-quadruplex (G4) structures. The heterodimeric POT1-TPP1 complex interacts specifically with telomere DNA to shield it from illicit DNA damage repair and to resolve secondary structure that impedes telomere extension. The mechanism by which POT1-TPP1 accomplishes these tasks is poorly understood. Here, we establish the kinetic framework for POT1-TPP1 binding and unfolding of telomere G4 DNA. Our data identify two modes of POT1-TPP1 destabilization of G4 DNA that are governed by protein concentration. At low concentrations, POT1-TPP1 passively captures transiently unfolded G4s. At higher concentrations, POT1-TPP1 proteins bind to G4s to actively destabilize the DNA structures. Cancer-associated POT1-TPP1 mutations impair multiple reaction steps in this process, resulting in less efficient destabilization of G4 structures. The mechanistic insight highlights the importance of cell cycle dependent expression and localization of the POT1-TPP1 complex and distinguishes diverse functions of this complex in telomere maintenance. (C) 2021 Elsevier Ltd. All rights reserved.
机译：染色体末端由富含鸟苷的端粒DNA保护，形成稳定的G-四链体（G4）结构。异二聚体POT1-TPP1复合物与端粒DNA特异性相互作用，保护其免受非法DNA损伤修复，并解析阻碍端粒延伸的二级结构。POT1-TPP1完成这些任务的机制尚不清楚。在这里，我们建立了POT1-TPP1结合和端粒G4 DNA去折叠的动力学框架。我们的数据确定了G4 DNA POT1-TPP1失稳的两种模式，它们受蛋白质浓度的控制。在低浓度下，POT1-TPP1被动捕获瞬时未折叠的G4s。在较高浓度下，POT1-TPP1蛋白与G4s结合，主动破坏DNA结构。与癌症相关的POT1-TPP1突变损害了该过程中的多个反应步骤，导致G4结构的不稳定效率降低。这一机制观点强调了POT1-TPP1复合物的细胞周期依赖性表达和定位的重要性，并区分了该复合物在端粒维持中的多种功能。（c）2021爱思唯尔有限公司保留所有权利。

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