CtIP-mediated fork protection synergizes with BRCA1 to suppress genomic instability upon DNA replication stress. Przetocka et al
In this study, we report a previously unrecognized function of CtIP in maintaining replication fork stability that is distinct from its role in DSB resection. In brief, we show that CtIP keeps DNA2 nuclease in check to limit degradation of stalled forks. Moreover, we find that loss of CtIP in BRCA1-deficient cells aggravates replication stress-induced genomic instability, causing synthetic lethality.