肿瘤放射抵抗与DNA损伤应答（DDR）关系密切。后期促进复合物APC、泛素连接酶RNF8等通过泛素-蛋白酶体途径调控DNA损伤的HR和NHEJ修复。我们既往研究发现：APCCdh1功能缺失导致NHEJ修复效率下降，增加肿瘤细胞的放射敏感性；既往报道RNF8通过介导Ku80的泛素化从而调控NHEJ修复。我们进一步研究结果提示：①RNF8主要在S/G2期募集，而Ku80主要在G1期募集；②RNF8在细胞周期中的表达模式及结构域分析提示其可能是APCCdh1的底物。因此我们提出假设：APCCdh1可能通过介导RNF8的泛素化降解，维持Ku80的稳定，从而保证NHEJ修复？本课题拟通过体内外实验验证APCCdh1对RNF8的泛素化修饰及对Ku80的间接调控，明确APCCdh1促进NHEJ修复的机制，完善DDR通路的理论基础，探索其对肿瘤放射治疗敏感性的影响，为肿瘤放疗增敏药物的开发提供新的思路。

Radioresistance of cancer is closely related to DNA damage response (DDR). Anaphase promoting complex(APC), E3 ubiquitin-protein ligase RNF8 regulate HR and NHEJ repair through ubiquitin-proteasome pathway in DNA damage. Our previous study revealed that the cells depleted of APCCdh1 showed a significence suppression of NHEJ repair efficiency and were sensitized to ioning radiation. It’s known that RNF8 mediates the ubiquitination of Ku80 and regulates NHEJ repair. Our previous results suggested: ①RNF8 was mainly recruited in S/G2 cells and Ku80 was mainly recruited in G1 cells; ②RNF8 protein expression pattern in the cell cycle and RNF8 sequence analysis suggested that it may be a substrate of APCCdh1. Therefore, we hypothesize that APCCdh1 promotes NHEJ repair through stabilizing Ku80 by ubiquitin-mediated degradation of RNF8. This study explores the role of APCCdh1 in NHEJ repair by direct regulation of RNF8 and indirect protection of Ku80, which will further improve the theoretical basis of DDR pathway and provide new ideas for the development of sensitizing agents for tumor radiotherapy.