DNA损伤的同源重组修复与肿瘤的发生和放化疗均存在密切的联系。MRE11是参与同源重组修复的关键因子，它的突变通常会导致对肿瘤的易感性增加。然而，是否存在调控MRE11的新型结合蛋白，及其与肿瘤放化疗之间是否存在必然的联系，目前尚不清楚。利用蛋白组学的方法，我们筛选并鉴别出了MRE11的新型结合蛋白C1QBP。预实验结果提示C1QBP可能通过影响MRE11进而正调控DNA损伤的同源重组修复，并且C1QBP的代偿性高表达可能是乳腺癌或卵巢癌对放化疗耐受的原因所在。在本项目中，我们将借助生物化学与细胞生物学相结合的手段，从无细胞体外反应体系、细胞、病理组织和动物模型等方面，深入研究C1QBP调控MRE11进而参与同源重组修复的分子机制，以及通过靶向干预C1QBP是否能够达到提高癌症放化疗效果的目的。以上问题的解答有助于提高我们对肿瘤发生机制的认识，对于临床上改善放化疗耐受，具有重要的指导意义。

DNA damage repair by homologous recombination (HR) is usually associated with tumorigenesis and radiochemotherapy. MRE11 is the key DNA damage repair factor in HR, and certain MRE11 mutations result in cancer predisposition. However, whether there are undefined MRE11 binding proteins regulating its function in HR, and how they are connected to cancer radiochemotherapy, are largely unknown. Here, by performing proteomics analyses, we unexpectedly identified C1QBP as a new MRE11 binding protein. Our preliminary data imply that C1QBP may regulate MRE11, and subsequently promote DNA damage repair by HR. This could explain why breast and ovarian cancers with highly expressed C1QBP are more tolerant of chemotherapy treatment. In this project, using the combined cell biology and biochemistry techniques from the levels of cell-free reconstitution system, cell, tumor tissue and mouse model, we will systematically investigate the underlying molecular mechanisms of C1QBP as a new MRE11 cofactor to upregulate DNA repair by HR, and whether the specific interference of C1QBP enhances breast or ovarian cancer’s sensitivity to chemotherapy treatment. Further exploration of this project will provide answers to the above questions, which will enrich our understanding of tumorigenesis and tumor treatment, and is valuable to improving cancer patients’ tolerance to radiochemotherapy clinically.