| Title | C1QBP Promotes Homologous Recombination by Stabilizing MRE11 and Controlling the Assembly and Activation of MRE11/RAD50/NBS1 Complex |
| Authors | Bai, Yongtai Wang, Weibin Li, Siyu Zhan, Jun Li, Hanxiao Zhao, Meimei Zhou, Xiao Albert Li, Shiwei Li, Xiaoman Huo, Yanfei Shen, Qinjian Zhou, Mei Zhang, Hongquan Luo, Jianyuan Sung, Patrick Zhu, Wei-Guo Xu, Xingzhi Wang, Jiadong |
| Affiliation | Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Radiat Med,Inst Syst Biomed, Beijing 100191, Peoples R China Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Anat Histol & Embryol, Beijing 100191, Peoples R China Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China Yale Univ, Sch Med, Dept Mol Biophys & Biochem, 333 Cedar St, New Haven, CT 06520 USA Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem & Struct Biol, San Antonio, TX 78229 USA Shenzhen Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Shenzhen 518060, Peoples R China |
| Issue Date | 2019 |
| Publisher | MOLECULAR CELL |
| Abstract | MRE11 nuclease forms a trimeric complex (MRN) with RAD50 and NBS1 and plays a central role in preventing genomic instability. When DNA double-strand breaks (DSBs) occur, MRN is quickly recruited to the damage site and initiates DNA end resection; accordingly, MRE11 must be tightly regulated to avoid inefficient repair or nonspecific resection. Here, we show that MRE11 and RAD50 form a complex (MRC) with C1QBP, which stabilizes MRE11/RAD50, while inhibiting MRE11 nuclease activity by preventing its binding to DNA or chromatin. Upon DNA damage, ATM phosphorylates MRE11-S676/S678 to quickly dissociate the MRC complex. Either excess or insufficient C1QBP impedes the recruitment of MRE11 to DSBs and impairs the DNA damage response. C1QBP is highly expressed in breast cancer and positively correlates with MRE11 expression, and the inhibition of C1QBP enhances tumor regression with chemotherapy. By influencing MRE11 at multiple levels, C1QBP is, thus, an important player in the DNA damage response. |
| URI | http://hdl.handle.net/20.500.11897/545092 |
| ISSN | 1097-2765 |
| DOI | 10.1016/j.molcel.2019.06.023 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
