Chromatin Assembly, Structure and Function

描述(申请人提供)：本研究的目的是了解 染色质组装、染色质结构与核的关系 功能。显然，染色质组装是一个基本的过程，即 对真核生物基因组的复制和维持至关重要。 在DNA合成之后，基因组必须快速而准确地组装 以将特定的染色质结构重新建立到子代 DNA链。即使染色质结构的细微变化也可以导致基因 功能障碍和疾病状态，如癌症。尽管它显然是全球性的 重要的是，人们对染色质组装的过程知之甚少。这个 在特定目标1中提出的研究将描绘染色质组装 可能由与生理相关的染色质介导的机制 组装因子RCAF(复制偶联组装因子)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 RCAF和CAF-1对这一进程的每一步所作的贡献。这些 染色质组装机制的生化研究将得到以下补充 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 基因分析，将在这方面提供一种连贯和有效的方法 染色质组装、结构和功能的新兴和令人兴奋的新领域。 此外，这项工作将影响基因表达，DNA修复， 复制和重组，可能为人类提供有价值的洞察 疾病状态，包括癌症，涉及这些重要的 染色质利用过程。

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.