ATM promotes reversed fork processing during DNA interstrand cross-link repair.

ABSTRACT: During replication-coupled DNA interstrand cross-link (ICL) repair, fork reversal is thought to enable the Fanconi anemia (FA) pathway to resolve the ICL through nucleolytic incisions. Subsequent fork restoration then allows nascent DNA strand extension past the lesion. Although these fork remodeling events are crucial for ICL repair, their regulation remains poorly understood. Here, we use cell-free Xenopus egg extracts to investigate fork dynamics during ICL repair by the FA pathway. We find that the ataxia telangiectasia-mutated (ATM) kinase is activated concomitantly with fork reversal and promotes resection of the reversed fork intermediate. This resection depends on the coordinated activities of the EXO1 and DNA2 nucleases. Our data indicate that EXO1 initiates 5' to 3' resect

SUBMITTER: Altshuller M 

PROVIDER: S-EPMC12632361 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature