| Title | Acetylation of p62 regulates base excision repair through interaction with APE1 |
| Authors | Li, Meiting Xiong, Jiannan Yang, Liqian Huang, Jie Zhang, Yu Liu, Minghui Wang, Lina Ji, Jianguo Zhao, Ying Zhu, Wei-Guo Luo, Jianyuan Wang, Haiying |
| Affiliation | Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Beijing Key Lab Prot Posttranslat Modificat & Cell, Beijing 100191, Peoples R China Peking Univ, Ctr Med Genet, Dept Med Genet, Hlth Sci Ctr, Beijing 100191, Peoples R China Peking Univ, Coll Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China Shenzhen Univ, Int Canc Ctr, Dept Biochem & Mol Biol, Guangdong Key Lab Genome Instabil & Human Dis Prev, Shenzhen 518055, Peoples R China |
| Keywords | DNA-DAMAGE SELECTIVE AUTOPHAGY PAGET-DISEASE PHOSPHORYLATION PATHWAY CANCER ELIMINATION ACTIVATION MECHANISMS SQSTM1/P62 |
| Issue Date | 19-Jul-2022 |
| Publisher | CELL REPORTS |
| Abstract | p62, a well-known adaptor of autophagy, plays multiple functions in response to various stresses. Here, we report a function for p62 in base excision repair that is distinct from its known functions. Loss of p62 impairs base excision repair capacity and increases the sensitivity of cancer cells to alkylating and oxidizing agents. In response to alkylative and oxidative damage, p62 is accumulated in the nucleus,acetylated by hMOF,and deacetylated by SIRT7, and acetylated p62 is recruited to chromatin. The chromatin-enriched p62 directly interacts with APE1, a key enzyme of the BER pathway, and promotes its endonuclease activity, which facil-itates BER and cell survival. Collectively, our findings demonstrate that p62 is a regulator of BER and provide further rationale for targeting p62 as a cancer therapeutic strategy. |
| URI | http://hdl.handle.net/20.500.11897/659154 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2022.111116 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 生命科学学院 |
