| Title | The deubiquitinase OTUD5 regulates Ku80 stability and non-homologous end joining |
| Authors | Li, Fangzhou Sun, Qianqian Liu, Kun Han, Haichao Lin, Ning Cheng, Zhongyi Cai, Yueming Tian, Feng Mao, Zebin Tong, Tanjun Zhao, Wenhui |
| Affiliation | Peking Univ, Dept Biochem & Mol Biol, Beijing Key Lab Prot Posttranslat Modificat & Cel, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China Peking Univ, Dept Lab Anim Sci, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China Jingjie PTM BioLab Co Ltd, Hangzhou 310018, Zhejiang, Peoples R China Peking Univ, Rheumat Immunol Dept, Shenzhen Hosp, Shenzhen 518035, Peoples R China |
| Keywords | XRCC5 DUBA DNA lesion Deubiquitinases library DNA damage response |
| Issue Date | 2019 |
| Publisher | CELLULAR AND MOLECULAR LIFE SCIENCES |
| Abstract | The ability of cells to repair DNA double-strand breaks (DSBs) is important for maintaining genome stability and eliminating oncogenic DNA lesions. Two distinct and complementary pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are employed by mammalian cells to repair DNA DSBs. Each pathway is tightly controlled in response to increased DSBs. The Ku heterodimer has been shown to play a regulatory role in NHEJ repair. Ku80 ubiquitination contributes to the selection of a DSB repair pathway by causing the removal of Ku heterodimers from DSB sites. However, whether Ku80 deubiquitination also plays a role in regulating DSB repair is unknown. To address this question, we performed a comprehensive study of the deubiquitinase specific for Ku80, and our study showed that the deubiquitinase OTUD5 serves as an important regulator of NHEJ repair by increasing the stability of Ku80. Further studies revealed that OTUD5 depletion impaired NHEJ repair, and hence reduced overall DSB repair. Furthermore, OTUD5-depleted cells displayed excess end resection; as a result, HR repair was facilitated by OTUD5 depletion during the S/G2 phase. In summary, our study demonstrates that OTUD5 is a specific deubiquitinase for Ku80 and establishes OTUD5 as an important and positive regulator of NHEJ repair. |
| URI | http://hdl.handle.net/20.500.11897/544906 |
| ISSN | 1420-682X |
| DOI | 10.1007/s00018-019-03094-5 |
| Indexed | SCI(E) |
| Appears in Collections: | 深圳医院 |
