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.

本研究报道了CtIP一项此前未被认知的功能：其可维持复制叉稳定性，且该功能与其在双链断裂（double-strand break, DSB）切除中的作用截然不同。简而言之，我们证实CtIP通过抑制DNA2核酸酶（DNA2 nuclease）的活性，以限制停滞复制叉的降解。此外，我们发现BRCA1缺陷型细胞中CtIP的缺失会加剧复制应激诱导的基因组不稳定性，进而引发合成致死效应。