Chromatin Assembly, Structure and Function

描述（由申请人提供）：本研究的目标是了解 染色质组装、染色质结构与细胞核 功能很明显，染色质组装是一个基本的过程， 对真核基因组的复制和维持至关重要。 在DNA合成之后，基因组必须快速准确地组装 在子细胞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会导致基因突变。 功能障碍和疾病状态，如癌症。尽管其明显的全球 重要的是，染色质组装的过程知之甚少。的 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（复制偶联组装因子）和CAF- 1 （染色质组装因子1）。这些实验将利用一个定义的 重组染色质组装系统，使我们能够检测 RCAF和CAF- 1对这一过程中的每一步作出的贡献。这些 染色质组装机制的生物化学研究将得到补充， 分子、细胞和遗传研究，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）。生物化学系统的独特性质，加上 遗传分析，将提供一个连贯和有效的方法，在这方面， 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，并可能提供有价值的洞察人类 疾病状态，包括癌症，涉及这些重要的缺陷， 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.