Acylpeptide hydrolase is a component of the cellular response to DNA damage.

•The cytosolic protease (APEH) is a component of the mammalian DNA damage response.•APEH interacts directly with XRCC1, a critical nuclear scaffold protein that accelerates DNA strand break repair.•XRCC1 interaction facilitates nuclear import/retention of APEH and recruitment to sites of oxidised chromatin.•APEH promotes repair of chromosomal DNA strand breaks and cellular resistance to oxidative stress.