基因组不间断受到内外因子的攻击而导致大量的DNA损伤，我们机体已经进化出一套高效的DNA损伤应答（DDR）系统来监测并修复受损的DNA，以维持基因组的稳定和防止疾病如癌症的发生。Polo样激酶PLK1是参与细胞周期调控的核心成员，然而DNA损伤发生后其活性调控机制一直不清楚。我们首次发现DNA损伤后，PARP1依赖的PLK1在DNA损伤位点快速募集，体外实验显示PLK1与多聚核糖基化链（PAR）的结合抑制其激酶活性；体外激酶实验显示检验点激酶CHK1对PLK1的S137位点磷酸化驱动其对Rad51磷酸化。本课题拟从分子、生化、细胞等层面剖析DNA损伤后PLK1活性被抑制、在S/G2期CHK1介导的PLK1部分激活的分子机制及其在DNA双链断裂修复中的功能，揭示PLK1在维持基因组稳定性及在肿瘤发生、发展中的作用。

Genomic DNA is constantly attacked by varieties of endogenous and environmental factors, generating millions of DNA damage per cell per day. Fortunately, our body has evolved a highly efficient DNA damage response system to recognize and repair the damaged DNA in order to maintain the genomic stability and prevent cells from diseases. Polo-like kinase1(PLK1) is an essential regulator in the cell cycle progression, however, the mechanism of tightly regulated kinase activity of PLK1 after DNA damage is largely unknown. We found for the first time that PLK1 is rapidly recruited to UV laser-induced DNA damage sties and this recruitment is dependent on poly ADP-ribose polymerase 1 (PARP1). In vitro binding assays revealed that PLK1 binds poly ADP-ribose chain (PAR), resulting in its kinase activity inhibition. In vitro kinase assays demonstrated that CHK1 phosphorylates PLK1 at S137, driving the subsequent phosphorylation of RAD51 by PLK1. This proposal will employ molecular, biochemical, and cellular approaches to determine the molecular mechanisms how the kinase activity of PLK1 is inhibited after DNA damage and reactivated by the checkpoint kinase CHK1 in S/G2 phase and how DNA damage-modulated PLK1 kinase activity has an impact on repair of DNA double strand breaks. These results in sum will reveal function of PLK1 in genome stability maintenance and tumorigenesis.