DEFINING A ROLE FOR BCP1 IN THE DNA DAMAGE RESPONSE OF SACCHAROMYCES CEREVISIAE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 基因组完整性的维持对所有生物体都是必不可少的，细胞对DNA损伤的反应是一系列紧密协调的事件，协调细胞周期停滞和DNA修复。本项目的总体目标是利用S.酿酒酵母作为模型系统，研究Bcp 1，在酵母中的必需蛋白的功能。Bcp 1是BCCIP的真菌同源物，BCCIP是一种最初通过与肿瘤抑制因子BRCA 2和细胞周期调节因子CDKN 1A（p21）相关而鉴定的蛋白质。在人类细胞中，BCCIP促进DNA损伤后的细胞周期停滞，并与BRCA 2一起参与同源重组修复。开始阐明Bcp 1在S.为了研究酿酒酵母DNA损伤反应，我们将研究Bcp 1定位于DNA损伤位点并有助于检查点激活导致细胞周期停滞的假设。提出了两个具体目的：1）分析Bcp 1在用DNA损伤剂处理的细胞中的定位和与染色质结合的蛋白质复合物的缔合，并确定Bcp 1的损失如何影响DNA修复或细胞存活，以及2）评估Bcp 1在响应于DNA损伤的检查点激活中的作用。这项研究的结果将提供深入了解Bcp 1的生物学功能及其对至关重要的DNA损伤反应的贡献。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Maintenance of genomic integrity is essential for all organisms, and cells respond to DNA damage with a tightly orchestrated sequence of events that coordinates cell cycle arrest and DNA repair. The overall objective of this project is to advance our understanding of this process, using S. cerevisiae as a model system to study the function of Bcp1, an essential protein in yeast. Bcp1 is the fungal homolog of BCCIP, a protein originally identified by its association with tumor suppressor BRCA2, and cell cycle regulator CDKN1A (p21). In human cells, BCCIP promotes cell cycle arrest following DNA damage, and participates in homologous recombination repair in conjunction with BRCA2. To begin to elucidate the role of Bcp1 in the S. cerevisiae DNA damage response, we will examine the hypothesis that Bcp1 localizes to sites of DNA damage and contributes to checkpoint activation leading to cell cycle arrest. Two Specific Aims are proposed: 1) Analyze Bcp1 localization and association with chromatin-bound protein complexes in cells treated with DNA damaging agents, and define how loss of Bcp1 impacts DNA repair or cell survival and 2) Evaluate a role for Bcp1 in checkpoint activation in response to DNA damage. The results of this study will provide insight as to the biological function of Bcp1 and its contribution to the critically important DNA damage response.