Structural mechanism of MRN-ATM in DNA double-strand break signalling and processing (18)

该项目旨在阐明DNA双链断裂是如何被Mre11-Rad50-Nbs1-ATM轴检测、信号传递和处理的。为了实现这一目标，我们将结合低温电子显微镜、生物化学和基于细胞的研究。特别是，我们将从功能和结构上剖析MRN的催化和支架作用，以便为其在双链断裂修复和染色质结构中鲜为人知的多效性功能提供分子机制。

This project aims at elucidating how DNA double-strand breaks are detected, signalled and processed by the Mre11-Rad50-Nbs1-ATM axis. To achieve this, we will use a combination of cryo-electron microscopy, bio-chemistry and cell-based studies. In particular, we will functionally and structurally dissect catalytic and scaffolding roles of MRN in order to provide molecular mechanisms for its poorly understood, pleiotropic func-tions in double-strand break repair and chromatin architecture.