Tip60是一个从酵母到哺乳动物高度保守的乙酰基转移酶，在DNA损伤修复中发挥着重要作用。我们前期研究发现，Tip60与细胞周期G2/M期关键调节分子Cyclin B1、Plk1存在直接的相互作用，并形成三元复合体定位到有丝分裂的中心体上，放射损伤也可诱导Tip60的SUMO-2/3化修饰。基于以上结果，我们拟开展以下研究：1.确定Tip60发生SUMO-2/3修饰的位点；2.确定Tip60 SUMO-2/3修饰的E3连接酶及去SUMO化酶；3.Tip60与SUMO-2/3、E3连接酶及去SUMO化酶在γ射线照射之后亚细胞定位及动态变化；4.Tip60的上述修饰对γ射线诱导的G2/M期检查点激活的调控机制。通过该课题研究，不仅可以阐明SUMO-2/3修饰对Tip60参与细胞周期调控及细胞周期检查点激活的调控机制，还可以为深入揭示放射损伤细胞基因组稳定性的调节机制及辐射防护提供新的理论基础。

Tip60, a very conserved acetyltransferase from yeast to mammalian cells, was proved to play very important role in DNA damage repair reponse. Our research has demonstrated that Tip60 interacts directly with Cyclin B1 and Plk1 and forms ternary complex to co-localize with them in centrosome of mitotic cells. It is the first time that Tip60 was found to participate in cell cycle control directly. As a post-translational modification, sumoylation was revealed to play essential roles in multiple signaling pathways,including DNA damage repair response. We found that Tip60 could be modified by SUMO-2/3 which is induced by ionizing radiation. Based on our previous work and these concepts, we plan to conduct the following research:1.Identification of the SUMO-2/3 modification site in Tip60; 2.Confirming the E3 ligase and deSUMOylation enzyme; 3.Confirming the sub-cellular localization of Tip60, SUMO-2/3, E3 ligase and deSUMOylation enzyme before and after different doses of γ-ray radiation; 4.investigate the role of Tip60 SUMO-2/3 modification in cell cycle control and radiation induced cell cycle G2/M chechpoint activation and the detailed mechanism. After fulfilling these aims, we will demonstrate the effect and molecular mechanism of Tip60 SUMO-2/3 modification in cell cycle G2/M checkpoint activation and further paved the way to deeply reveal the mechanism of genome stability of radiation damaged cells and to develop new-concept radiation protection drugs.