Reference - PMID:30104346 - Mre11 complex links sister chromatids to promote repair of a collapsed replication fork.
Reference summary
- PubMed ID
- PMID:30104346
- Title
- Mre11 complex links sister chromatids to promote repair of a collapsed replication fork.
- Authors
- Zhu M, Zhao H, Limbo O, Russell P
- Citation
- Proc Natl Acad Sci U S A 2018 Aug 28;115(35):8793-8798
- Publication year
- 2018
- Abstract
- Collapsed replication forks, which are a major source of DNA double-strand breaks (DSBs), are repaired by sister chromatid recombination (SCR). The Mre11-Rad50-Nbs1 (MRN) protein complex, assisted by CtIP/Sae2/Ctp1, initiates SCR by nucleolytically resecting the single-ended DSB (seDSB) at the collapsed fork. The molecular architecture of the MRN intercomplex, in which zinc hooks at the apices of long Rad50 coiled-coils connect two Mre11 2 -Rad50 2 complexes, suggests that MRN also structurally assists SCR. Here, Rad50 ChIP assays in Schizosaccharomyces pombe show that MRN sequentially localizes with the seDSB and sister chromatid at a collapsed replication fork. Ctp1, which has multivalent DNA-binding and DNA-bridging activities, has the same DNA interaction pattern. Provision of an intrachromosomal repair template alleviates the nonnucleolytic requirement for MRN to repair the broken fork. Mutations of zinc-coordinating cysteines in the Rad50 hook severely impair SCR. These data suggest that the MRN complex facilitates SCR by linking the seDSB and sister chromatid.
