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.

真核生物的基因组作为染色质存在。染色质的组织提供了一种调节对基本遗传信息的访问的方法。真核生物调节染色质构象的一种方法是通过染色质重塑运动蛋白的作用。 SWI/SNF重塑复合物的人类形式是一系列染色质重塑ATPases，其中约15个部分重叠的亚基。这些复合物主要在增强子方面发挥作用，并且已经观察到在一系列人类癌症中以高速率突变。这些复合物活性的生化和结构表征有限。该建议旨在使用从昆虫细胞纯净的重组蛋白来解决此问题。冷冻电子显微镜将用于表征复合物的结构。将使用在模型DNA模板上组装的核小体进行生化测定。洞悉这些复合物的结构和功能将有助于确定由有缺陷的复合物驱动的癌细胞中脆弱性。项目提供跨学科技能的培训。