Human SNM1A and XPF–ERCC1 collaborate to initiate DNA interstrand cross-link repair

Abstract

One of the major mammalian DNA interstrand cross-link (ICL) repair pathways is coupled to replication. Here, the 5′–3′ exonuclease activity of SNM1A is found to be critical for ICL repair. Following a 5′ incision of the cross-link by XPF–ERCC1, SNM1A loads at the nick and digests past the ICL, initiating the repair process. Failure of this XPF–ERCC1- and SNM1A-dependent repair pathway causes Mus81-induced replication fork cleavage and double strand breaks, leading to ICL sensitivity