SUMO化修饰调控hSSB1的机制，功能及临床意义

单链DNA结合蛋白1（hSSB1）在DNA损伤应答中发挥重要功能，其缺失会引起细胞周期检测点的失活，增加肿瘤细胞的放化疗敏感性。但hSSB1自身是如何被调控的，目前研究甚少,我们团队已表明，p300介导的乙酰化可增强hSSB1的稳定性。最近我们发现: hSSB1中K79和K94这两个位点被SUMO化修饰，且在DNA损伤情况下，该SUMO化水平显著升高，同时促进了hSSB1与DNA损伤应答中关键蛋白NBS1的结合。本项目拟进一步明确hSSB1被SUMO化修饰及其在DNA损伤应答中的生物学意义；鉴定hSSB1的SUMO E3连接酶和SUMO特异蛋白酶(SENPs)；探讨hSSB1的SUMO修饰是否参与肿瘤细胞的放化疗敏感性。本项目的完成，将明确hSSB1被SUMO化修饰的生物学基础和意义，拓展hSSB1作为肿瘤治疗的潜在靶点，为SUMO化抑制剂作为放化疗增敏剂的临床应用提供实验依据。

Human single-stranded DNA binding protein 1 (hSSB1) has been shown to play crucial roles in DNA damage response. Depletion of hSSB1 in cells would induce defective cell cycle checkpoint activation and increased chemo- or radiosensitivity. However, it is largely unknown how hSSB1 itself is regulated. Our group has reported that acetylation of hSSB1 by p300 increases its stability. Here, our preliminary data show that DNA damage promotes the SUMOylation of hSSB1 on lysine 79 and 94, and that this SUMOylation of hSSB1 increase its interaction with NBS1, a key protein involved in DNA damage response. This proposal aims to further understand the biological significance of hSSB1 SUMOylation under DNA damage, identify its SUMO E3 ligase and SUMO-specific protease, explore the involvement of SUMOylation in chemo- or radiosensitivity. We believe that our research would demonstrate the biological process and significance of SUMOylation on hSSB1, explore the possibility of hSSB1 as therapeutic target, and provide experimental support for SUMOylation inhibitor as sensitizer for chemo- or radiotherapy.