DNA双链断裂(DSB)是细胞内最致命的一种损伤，主要通过同源重组（HR）和非同源末端连接（NHEJ）两条途径进行修复。53BP1-RIF1和BRCA1-CtIP通过拮抗控制断裂末端剪切调控修复通路的选择。已知53BP1-RIF1-shieldin能部分阻碍剪切，但具体分子机制仍然未知。我们鉴定出一个新的RIF1结合蛋白Raib，其作用于RIF1的下游参与NHEJ通路拮抗BRCA1功能，使癌细胞对于抗癌药物olaparib更敏感。此外，Raib可招募异染色质形成蛋白HP1γ到损伤位点。我们将从Raib蛋白是否帮助形成损伤位点临近高级染色质结构入手研究其抑制末端剪切的机制。本课题的研究将为人们理解末端保护机制提供一个全新的视角，有希望对DSB修复调控领域末端保护这一未解难题给出答案，同时有助于阐明部分癌细胞对抗癌药物的耐药机制，优化治疗方法。

DNA double-strand break (DSB) is one of the most toxic damage to cells. The improper repair of DSB will result in chromosomal variation and lead to cancer, aging and other diseases. In order to repair correctly, cells must choose from two incompatible major repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR), which is essential for maintaining genome stability. 53BP1-RIF1 and BRCA1-CtIP regulate the selection of repair pathway through antagonistic control of the end resection. It is known that 53BP1-RIF1-shieldin can partially block the end resection and inhibit HR pathway, but the molecular mechanism is still unknown. In our project, we identified a new RIF1 binding protein Raib by immunoprecipitation combined with mass spectrometry. The primary results showed that Raib was involved in NHEJ pathway to antagonize BRCA1 function in the downstream of RIF1, which made cancer cells more sensitive to olaparib. In addition, Raib could recruit HP1 γ to the damage site. We will study whether Raib can protect the broken ends by promoting the formation of chromatin three-dimensional topological structure. This research will provide a new perspective for people to understand the mechanism of end protection, and also show the necessity of chromatin 3D structure for DNA damage repair. It is hoped to give an answer to the unsolved problem of end protection in the field of DSB repair, and help to clarify the mechanism of resistance of some cancer cells to anticancer drugs and optimize the treatment methods.