Acetylation of p62 regulates base excision repair through interaction with APE1

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.

Automated summary

The study reveals a new function of p62 in base excision repair, distinct from its known functions. Loss of p62 impairs repair capacity and increases cancer cell sensitivity to alkylating and oxidizing agents. Therefore, targeting p62 may have potential for cancer therapeutics.