DNA 双链断裂 (DSB) 是辐射致基因组不稳定性的主要原因，同源重组（HR）是DSB修复主要方式，但参与HR修复调控分子机制总体还未完全阐明。丝氨酸/苏氨酸激酶Plk1可通过磷酸化HR修复重要的调控分子RAD51、BRCA1来参与HR修复，但电离辐射后Plk1上游调节因子尚未明确。我们前期研究发现，非受体酪氨酸激酶c-Abl可与Plk1直接相互作用；特异磷酸化Plk1；促进Plk1蛋白表达及激酶活性。而文献报道，辐射后c-Abl激酶活性增强。这些结果提示，辐射后c-Abl可调节Plk1表达及激酶活性，调控HR修复，从而增强基因组稳定性。为证实该假说，本项目将验证辐射后c-Abl对Plk1表达及激酶活性的影响；研究c-Abl对Plk1的磷酸化在HR修复中作用；探讨辐射后c-Abl促进Plk1表达分子机制。该研究将加深对细胞基因组稳定性调控机制认识，为辐射损伤防护机制研究提供新的理论依据。

DNA double strand break (DSB) is the major reason of genomic instability induced by radiation. Homologous recombination (HR) is the main way of DSB repair, but the molecular mechanism regulation of HR repair is not completely clear. Serine/threonine kinase Plk1 is involved in HR repair by phosphorylating RAD51 and BRCA1, the important regulator molecules of HR repair. But after ionizing radiation, the upstream regulatory factor of Plk1 is not definited. Our previous studies found that non receptor tyrosine kinase c-Abl can interact with Plk1 and can specifically phosphorylate Plk1, thus regulating the level and activity of this kinase. These results suggested that activated c-Abl after radiation might regulate the level and kinase activity of Plk1, mediating HR repair and therefore to enhance genomic stability. To confirm the hypothesis, we will make sure the effect of c-Abl on the level and kinase activity of Plk1 after radiation, and investigate the role of phosphorylation of Plk1 by c-Abl in the HR repair. Finally, we will explore the molecular mechanism of c-Abl promoting the level of Plk1 after radiation. The further research by the project will deepen our understanding of the genomic stability regulation mechanism and provide a new theoretical basis for the radiation protection.