Acetylation of p62 regulates base excision repair through interaction with APE1

Meiting Li; Jiannan Xiong; Liqian Yang; Jie Huang; Yu Zhang; Minghui Liu; Lina Wang; Jianguo Ji; Ying Zhao; Wei-Guo Zhu; Jianyuan Luo; Haiying Wang

doi:10.1016/j.celrep.2022.111116

Acetylation of p62 regulates base excision repair through interaction with APE1

Cell Rep. 2022 Jul 19;40(3):111116. doi: 10.1016/j.celrep.2022.111116.

Authors

Meiting Li¹, Jiannan Xiong², Liqian Yang², Jie Huang², Yu Zhang³, Minghui Liu³, Lina Wang², Jianguo Ji⁴, Ying Zhao², Wei-Guo Zhu⁵, Jianyuan Luo⁶, Haiying Wang⁷

Affiliations

¹ Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Medical Genetics, Center for Medical Genetics, Peking University Health Science Center, Beijing 100191, China.
² Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
³ Department of Medical Genetics, Center for Medical Genetics, Peking University Health Science Center, Beijing 100191, China.
⁴ State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China.
⁵ Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University School of Medicine, Shenzhen 518055, China.
⁶ Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Medical Genetics, Center for Medical Genetics, Peking University Health Science Center, Beijing 100191, China. Electronic address: luojianyuan@bjmu.edu.cn.
⁷ Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: wendy@bjmu.edu.cn.

PMID: 35858573
DOI: 10.1016/j.celrep.2022.111116

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 facilitates 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.

Keywords: APE1; CP: Molecular biology; SIRT7; acetylation; base excision repair; hMOF; p62.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation
Cell Survival
Chromatin
DNA Damage
DNA Repair*
DNA-(Apurinic or Apyrimidinic Site) Lyase* / genetics
DNA-(Apurinic or Apyrimidinic Site) Lyase* / metabolism

Substances

Chromatin
DNA-(Apurinic or Apyrimidinic Site) Lyase