Structural and biochemical characterisation of human SWI/SNF-related chromatin remodelling complexes

人类 SWI/SNF 相关染色质重塑复合物的结构和生化特征

• 批准号: 1914302
• 金额: --
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1914302
• 关键词: Structural; biochemical; characterisation; human; SWI

The genomes of eukaryotes exist as chromatin. The organisation of chromatin provides a means of regulating access to the underlying genetic information. One way in which eukaryotes regulate chromatin conformation is through the action of chromatin remodelling motor proteins. Human forms of the SWI/SNF remodelling complex are a series of chromatin remodelling ATPases comprised of some 15 partially overlapping subunits. These complexes function predominantly at enhancers and have been observed to be mutated at high rates in a range of human cancers. Biochemical and structural characterisation of the activities of these complexes is limited. This proposal aims to address this using recombinant expressed proteins purified from insect cells. Cryo-electron microscopy will be used to characterise the structure of the complexes. Biochemical assays will be performed using nucleosomes assembled on model DNA templates. Insight into the structure and function of these complexes will help identify vulnerabilities in cancer cells where proliferation is driven by defective complexes. Project provides training in Interdisciplinary Skills.

真核生物的基因组以染色质的形式存在。染色质的组织提供了一种对潜在遗传信息的获取进行调控的方法。真核生物调节染色质构象的一种方式是通过染色质重塑马达蛋白的作用。人的SWI/SNF重塑复合体是由大约15个部分重叠的亚基组成的一系列染色质重塑ATPase。这些复合体主要作用于增强剂，并已被观察到在一系列人类癌症中以高速率突变。对这些络合物活性的生化和结构表征是有限的。这项提议旨在利用从昆虫细胞中纯化的重组表达蛋白来解决这一问题。低温电子显微镜将被用来表征这些络合物的结构。生化分析将使用组装在模型DNA模板上的核小体进行。深入了解这些复合体的结构和功能将有助于识别癌细胞中由有缺陷的复合体驱动增殖的脆弱性。该项目提供跨学科技能培训。