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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 保持基因组的完整性对所有生物体来说都是必不可少的，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促进我们对这一过程的理解，以酿酒酵母为模型系统来研究Bcp1的功能，Bcp1是酵母中的一种必不可少的蛋白质。Bcp1是BCCIP的真菌同源物，BCCIP最初是一种蛋白质，它与肿瘤抑制因子BRCA2和细胞周期调节因子CDKN1A有关。在人类细胞中，BCCIP促进DNA损伤后的细胞周期停滞，并与BRCA2一起参与同源重组修复。为了开始阐明Bcp1在酿酒酵母DNA损伤反应中的作用，我们将检验Bcp1定位于DNA损伤部位并有助于检查点激活导致细胞周期停滞的假设。提出了两个特定的目标：1)分析Bcp1在DNA损伤剂处理的细胞中的定位及其与染色质结合蛋白复合体的关联，并确定Bcp1的缺失如何影响DNA修复或细胞存活；2)评估Bcp1在DNA损伤反应中检查点激活中的作用。这项研究的结果将为深入了解Bcp1的生物学功能及其在至关重要的DNA损伤反应中的作用提供依据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. 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.