HISTONE NUCLEAR IMPORT AND CHROMATIN ASSEMBLY

描述（由申请人提供）：本项目的长期目标是 了解组蛋白和染色质相关因子的核输入 是受调控的，并阐明如何核输入和染色质的过程 会议协调。每一个细胞周期细胞的整个DNA含量 必须快速复制并重新包装成核小体。组蛋白是 建议遵循一个特定的和高度调节的细胞质过程， 翻译后修饰，核导入和递送，然后 组装成染色质。该项目的重点是重要的问题， 核进口因素是否对进口以外的进程进行管制，例如 核内递送和组蛋白复合物的组装。此外还将 测试组蛋白修饰酶和染色质组装因子是否调节 核进口，在这些过程之间提供协调联系。 具体来说，酵母细胞质的翻译后修饰 将确定组蛋白及其在进口调节中的重要性， 考察假设细胞质中组蛋白的修饰 通过影响组蛋白与 具体运输因素。核小体组装蛋白（Nap1p） 将测试组蛋白导入中的蛋白质，以确定这种蛋白质是否有助于 组蛋白H2A和H2B与特定输入因子的关联。的 RanGTP介导的组蛋白从其上解离的要求 将调查相关的进口因素。假设将被检验， 组蛋白与Kaps的解离受翻译后 修饰和染色质组装因子。这可能是一种机制， 调节组蛋白向染色质装配的空间和时间递送 复制分叉处的因素。核小体的正确组装是 对于维持所有真核细胞中的基因组稳定性至关重要。的 参与核小体组装和重塑的蛋白质功能障碍 这些通路也与人类疾病和癌症相一致。这凸显 理解组蛋白的作用机制至关重要。 进入细胞核并组装成染色质，以及这些过程如何 是协调的。

DESCRIPTION (provided by applicant):The long term goal of this project is to understand how the nuclear import of histones and chromatin-associated factors is regulated, and elucidate how the processes of nuclear import and chromatin assembly are coordinated. Every cell cycle the entire DNA content of a cell must be rapidly replicated and repackaged into nucleosomes. Histones are proposed to follow a specific and highly regulated process of cytoplasmic post-translational modification, nuclear import and delivery, followed by assembly into chromatin. This project focuses on the significant question of whether nuclear import factors regulate processes beyond import, such as the intranuclear delivery and assembly of histone complexes. In addition, it will test whether histone modifying enzymes and chromatin assembly factors regulate nuclear import, providing a co-ordinate link between these processes. Specifically, the cytoplasmic post translational modifications of yeast histones will be identified and their importance in the regulation of import examined. The hypothesis is that modification of histones in the cytoplasm plays a regulatory role in transport by affecting association of histones with specific transport factors. The role of the nucleosome assembly protein (Nap1p) in histone import will be tested to determine whether this protein facilitates the association of histones H2A and H2B with a specific import factor. The requirements for the RanGTP-mediated dissociation of histones from their cognate import factors will be investigated. The hypothesis will be tested that the dissociation of histones from the Kaps is regulated by post-translational modifications and chromatin assembly factors. This may be a mechanism to regulate the spatial and temporal delivery of histones to chromatin assembly factors at the replication fork. The correct assembly of nucleosomes is critical for maintaining genomic stability in all eukaryotic cells. The dysfunction of proteins involved in the nucleosome assembly and remodeling pathways is also coincident with human disease and cancer. This highlights the fundamental importance of understanding the mechanisms by which histones are imported into the nucleus and assembled into chromatin, and how these processes are coordinated.