内源和外源因素持续对细胞中基因组DNA造成损伤。正常细胞通过DNA修复系统和细胞周期监控点系统的协调作用有效修复这些损伤，维持基因组稳定性。当DNA修复系统或/和细胞周期监控点系统基因突变，会导致高水平DNA损伤，并由此导致癌症等疾病的发生。过去的研究表明，由Rad9、Hus1和Rad1构成的9-1-1三聚复合体在细胞周期监控点和多种DNA损伤修复（直接回复、碱基切除、错配和同源重组修复）中发挥重要作用。我们最近的前期研究显示：（1）Rad9在DNA双链断裂非同源末端连接修复中也起重要作用；（2）Rad9与该修复中的关键蛋白质Ku70相互作用。我们将在该申请项目中研究Rad9参与DNA双连断裂非同源末端连接修复的分子机理。

Endogenous and enviromental factors constantly causes genomic DNA lesions in cells. In normal cells, DNA repair and cell cycle checkpoint control systems coordinately and efectively repair these lesions and maintain genomic integrity. Malfunctional mutations of the genes in DNA repair and cell cycle checkpoint control systems can cause high levels of DNA lesions leading to severe diseases such as cancer. Previous studies show that the ring-like 9-1-1 protein complex composed of Rad9, Hus1 and Rad1 plays important roles in cell cycle checkpoint controls and a few DNA repair pathways (direct damage reverse, base excision repair， mismatch repair and homologous recombination repair). Our recent preliminary work has demonstrated that (1)Rad9 also plays an important role in nomhomologous endjoining (NHEJ) double strand DNA repair, and (2) Rad9 physically interacts with the key NHEJ protein factor Ku70. We will investigate the role of Rad9 and its molecular mechanisms in this proposed study.