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进口 并阐明了核进口和染色质的过程是如何 装配是协调一致的。每个细胞周期一个细胞的全部DNA含量 必须快速复制并重新包装成核小体。组蛋白是 建议遵循特定和高度调控的细胞质过程 翻译后修改、核进口和交付，随后 组装成染色质。这个项目关注的是 核进口因素是否规范进口以外的过程，如 组蛋白复合体的核内递送和组装。此外，它还将 检验组蛋白修饰酶和染色质组装因子是否调节 核进口，提供了这些进程之间的协调联系。 具体来说，酵母的细胞质翻译后修饰 将确定组蛋白及其在进口调节中的重要性 检查过了。假设是细胞质中组蛋白的修饰 通过影响组蛋白与组蛋白的联系，在运输中起到调节作用 特定的运输因素。核小体组装蛋白(Nap1p)的作用 将对组蛋白导入进行测试，以确定该蛋白是否有助于 组蛋白H_2A和H_2B与特定的输入因子之间的联系。这个 RanGTP介导的组蛋白从其上解离的要求 将对同类进口因素进行调查。这一假设将得到检验， 组蛋白与KAP的解离受翻译后调控 修饰和染色质组装因子。这可能是一种机制，可以 调控组蛋白向染色质组装的时空递送 复制分叉的因素。核小体的正确组装是 在所有真核细胞中维持基因组稳定性的关键。这个 参与核小体组装和重塑的蛋白质功能障碍 通路也与人类疾病和癌症重合。这突出了 了解组蛋白的作用机制具有重要意义 进入细胞核并组装成染色质，以及这些过程是如何进行的 是协调一致的。

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.