Chromatin Assembly, Structure and Function

染色质组装、结构和功能

• 批准号: 6417728
• 负责人: Jessica K Tyler
• 金额: $ 25.67万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6417728
• 关键词: DNA; DNA repair; DNA replication; acetylation; cell component structure /function; cell cycle; cell nucleus; chromatin; chromosomes; cytogenetics; eukaryote; flow cytometry; fungal genetics; gene expression; genetic recombination; genome; histones; microarray technology; nucleosomes; polymerase chain reaction; telomere; yeasts

DESCRIPTION (provided by applicant): The goal of this research is to understand the relationship between chromatin assembly, chromatin structure and nuclear function. It is clear that chromatin assembly is a fundamental process that is essential for the replication and maintenance of the eukaryotic genome. Following DNA synthesis, the genome must be rapidly and accurately assembled into chromatin to re-establish specific chromatin structures onto the daughter DNA strands. Even subtle changes in chromatin structure can lead to gene dysfunction and to disease states, such as cancer. Despite its obvious global importance, the process of chromatin assembly is poorly understood. The research proposed in Specfic Aim 1 will delineate the chromatin assembly mechanism that is mediated by the putative physiologically relevant chromatin assembly factors RCAF (replication-coupling assembly factor) and CAF- 1 (chromatin assembly factor 1). These experiments will utilize a defined recombinant chromatin assembly system that permits us to detect the contribution that RCAF and CAF- 1 make to each step in the process. These biochemical studies of the chromatin assembly mechanism will be complemented by molecular, cellular, and genetic studies to test the hypothesis that RCAF and CAF- 1 are directly involved in the assembly of chromatin in budding yeast (Specific Aim 2). The unique nature of the biochemical system, coupled with the genetic analyses, will provide a coherent and effective approach in this emerging and exciting new area of chromatin assembly, structure and function. In addition, this work will impact the fields of gene expression, DNA repair, replication and recombination and may provide valuable insight into human disease states, including cancer that involve defects in these important chromatin-utilizing processes.

描述（由申请人提供）：本研究的目标是了解 染色质组装、染色质结构和核之间的关系 功能。很明显，染色质组装是一个基本过程 对于真核基因组的复制和维持至关重要。 DNA 合成后，必须快速准确地组装基因组 进入染色质以在女儿身上重建特定的染色质结构 DNA 链。即使是染色质结构的细微变化也可能导致基因突变 功能障碍和疾病状态，例如癌症。尽管其明显的全球性 重要性，但人们对染色质组装过程知之甚少。这 具体目标 1 中提出的研究将描绘染色质组装 由假定的生理相关染色质介导的机制 组装因子RCAF（复制耦合组装因子）和CAF-1 （染色质组装因子 1）。这些实验将利用定义的 重组染色质组装系统使我们能够检测 RAF 和 CAF-1 对该过程中每个步骤的贡献。这些 染色质组装机制的生化研究将得到补充 分子、细胞和遗传学研究，以检验 RCAF 和 CAF-1 直接参与芽殖酵母染色质的组装 （具体目标 2）。生化系统的独特性质，加上 遗传分析将为此提供连贯有效的方法 染色质组装、结构和功能的新兴且令人兴奋的新领域。 此外，这项工作还将影响基因表达、DNA 修复、 复制和重组，可能为人类提供有价值的见解 疾病状态，包括涉及这些重要缺陷的癌症 染色质利用过程。