Functional and structural dissection of the human replisome

人类复制体的功能和结构剖析

• 批准号: DE240100780
• 负责人: Dr Jacob Lewis
• 金额: $ 31.51万
• 依托单位: University of Wollongong
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Early Career Researcher Award
• 财政年份: 2024
• 资助国家: 澳大利亚
• 起止时间: 2024-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DE240100780
• 关键词: Functional; structural; dissection; human; replisome

This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecular visualisation technologies, leading to the first molecular description of dynamic processes used by the human replisome. Benefits include improved understanding of a fundamental biological process that often malfunctions in cancers, development of novel methodology, and interdisciplinary training.

该项目旨在开发技术来可视化人类复制体的结构和酶活性，复制体是在细胞分裂前复制DNA的多蛋白质组装体。一个新的单分子和国家的最先进的冷冻电子显微镜的组合将被用来定义如何在复制应激的时间，人类复制体协调DNA合成。该项目的主要成果包括开发新的分子可视化技术，导致人类复制体使用的动态过程的第一个分子描述。好处包括提高对癌症中经常发生故障的基本生物过程的理解，开发新的方法和跨学科培训。