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.

在本项研究中，我们揭示了CtIP在维持复制叉稳定性方面的一项先前未识别的功能，该功能与其在DNA单链断裂修复中的作用截然不同。简而言之，我们证明了CtIP能够有效调控DNA2核酸酶活性，以限制停滞复制叉的降解。此外，我们发现CtIP在BRCA1缺陷细胞中的缺失加剧了复制压力引发的基因组不稳定，进而导致合成致死。