Structure-function analyses of mammalian Timeless in genome maintenance (10)

哺乳动物 Timeless 在基因组维护中的结构功能分析 (10)

• 批准号: 418752028
• 金额: --
• 依托单位: Arbeitsgruppe Strukturelle Chronobiologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418752028?language=en
• 关键词: Structure; function; analyses; mammalian; Timeless

Mammalian Timeless (Tim) and the Timeless-interacting protein (Tipin) are components of the replica-tion fork protection complex. To provide mechanistic insights into their functions in genome mainte-nance, we will analyse 3D structures of Tim, Tipin and their complexes with single-stranded DNA-binding RPA or DNA, using an integrated structural biology approach that includes X-ray crystallog-raphy, single particle cryo-electron microscopy, small angle X-ray scattering and crosslinking mass spectrometry. These studies will be complemented by cell-based in vivo functional analyses in order to advance our mechanistic understanding of replication stress signalling and fork protection.

哺乳动物Timeless（Tim）和Timeless-interacting protein（Tipin）是复制叉保护复合物的组成部分。为了提供对它们在基因组维护中的功能的机理性见解，我们将使用包括X射线晶体学、单粒子冷冻电子显微镜、小角X射线散射和交联质谱的综合结构生物学方法来分析Tim、Tipin及其与单链DNA结合RPA或DNA的复合物的3D结构。这些研究将通过基于细胞的体内功能分析来补充，以促进我们对复制应激信号传导和叉保护的机制理解。