Mechanistic Analysis of Chromatin Remodeling

染色质重塑的机制分析

• 批准号: 7595778
• 负责人: GEETA J NARLIKAR
• 金额: $ 24.59万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7595778
• 关键词: ATP Hydrolysis; ATP phosphohydrolase; Address; Affect; Affinity; Binding; Biochemical; Biology; Catalytic Domain; Cell Cycle; Chromatin; Chromatin Remodeling Factor; Chromatin Structure; Chromosome Structures; Complex; Coupled; Coupling; DNA; Data; Defect; Development; Enzymatic Biochemistry; Enzymes; Event; Fluorescence; Fluorescence Resonance Energy Transfer; Genes; Genetic Transcription; Goals; Histones; Hydrolysis; Individual; Kinesin; Kinetics; Lead; Malignant Neoplasms; Measures; Methods; Molecular; Molecular Conformation; Molecular Machines; Mutation; Myosin ATPase; Nuclear; Nucleosomes; Nucleotides; Play; Process; Reaction; Regulation; Relative (related person); Reporting; Role; SMARCA4 gene; Thermodynamics; Time; Transcription Process; Transcriptional Regulation; Work; base; chromatin remodeling; dimer; hSWI/SNF; helicase; insight; promoter; recombinational repair; research study; restriction enzyme; tool

DESCRIPTION (provided by applicant) The packaging of DMA into chromatin makes it largely inaccessible for the central nuclear processes of transcription, replication, recombination and repair. ATP-dependent chromatin remodeling complexes play a key role in making chromatin dynamic. However, the mechanisms by which these complexes function are largely unknown. The overall goal of this proposal is to use the tools of mechanistic enzymology to understand how a major ATP-dependent chromatin remodeling complex, human SWI/SNF, catalyzes exposure of DMA from chromatin. SWI/SNF complexes play crucial roles in the transcriptional regulation of several genes as well in the cell cycle based regulation of chromosome structure. Consistent with these roles, mutations in the components of these complexes are associated with severe developmental defects and a variety of cancers. A detailed understanding of SWI/SNF mechanism will provide insights into how its activity is regulated and how it malfunctions. The specific aims of this project are: (1) To identify the individual steps in chromatin remodeling that lead to stable exposure of DNA. (2) To determine how SWI/SNF uses the energy of ATP binding and hydrolysis for remodeling chromatin. (3) To dissect the mechanistic contributions of individual SWI/SNF subunits.

描述（由申请人提供）DNA包装到染色质中使其在很大程度上无法进入转录、复制、重组和修复的中心核过程。ATP依赖的染色质重塑复合物在使染色质动态化中起关键作用。然而，这些复合物的功能机制在很大程度上是未知的。本提案的总体目标是使用机械酶学的工具来了解主要的ATP依赖性染色质重塑复合物，人SWI/SNF，如何催化染色质中的DMA暴露。SWI/SNF复合物在几个基因的转录调控以及基于细胞周期的染色体结构调控中起关键作用。与这些作用一致，这些复合物组分的突变与严重的发育缺陷和各种癌症有关。对SWI/SNF机制的详细了解将有助于深入了解其活动是如何调节的以及如何发生故障。本项目的具体目标是：（1）确定导致DNA稳定暴露的染色质重塑的各个步骤。(2)确定SWI/SNF如何利用ATP结合和水解的能量重塑染色质。(3)剖析单个SWI/SNF亚基的机制贡献。