AI Article Synopsis
- Protecting stalled DNA replication forks is vital for preventing genomic instability, which can lead to cancer.
- Various proteins involved in DNA repair, especially in homologous recombination, also help stabilize these stalled forks.
- CtIP, along with BRCA1, plays a crucial role in shielding these forks from degradation, highlighting its important function beyond traditional roles in double-strand break repair.
Article Abstract
Protecting stalled DNA replication forks from degradation by promiscuous nucleases is essential to prevent genomic instability, a major driving force of tumorigenesis. Several proteins commonly associated with the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) have been implicated in the stabilization of stalled forks. Human CtIP, in conjunction with the MRE11 nuclease complex, plays an important role in HR by promoting DSB resection. Here, we report an unanticipated function for CtIP in protecting reversed forks from degradation. Unlike BRCA proteins, which defend nascent DNA strands from nucleolytic attack by MRE11, we find that CtIP protects perturbed forks from erroneous over-resection by DNA2. Finally, we uncover functionally synergistic effects between CtIP and BRCA1 in mitigating replication-stress-induced genomic instability. Collectively, our findings reveal a DSB-resection- and MRE11-independent role for CtIP in preserving fork integrity that contributes to the survival of BRCA1-deficient cells.
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| http://dx.doi.org/10.1016/j.molcel.2018.09.014 | DOI Listing |
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