Minimal Resection Takes Place during Break-Induced Replication Repair of Collapsed Replication Forks and Is Controlled by Strand Invasion

摘要

A natural and frequently occurring replication problemis generated by the action of topoisomerase I(Top1). Trapping of Top1 in a cleavage complex onthe DNA generates a protein-linked DNA nick (PDN),which upon DNA replication can be transformedinto a one-ended double-strand break (DSB). Breakinducedreplication (BIR) has been recognized as acritical repair mechanism of one-ended DSBs. Here,we have investigated resection at a one-ended DSBformed exclusively during replication due to Top1-mimicking damage. We show that resection is minimal,and only when strand invasion is abolished isextensive resection detected. When DNA synthesisis slowed by hydroxyurea treatment, extended resectionis not observed, which suggests that strand invasionand/or heteroduplex formation restrains resection.Our results demonstrate that the BIR pathwayacting during S phase is tailored to prevent hazardouseffects of naturally and frequently occurring DNAbreaks such as Top1-generated PDNs.