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Smc5/6 maintains stalled replication forks in a recombination-competent conformation
journal contribution
posted on 2023-06-07, 14:57 authored by Anja Irmisch, Eleni Ampatzidou, Ken'ichi Mizuno, Matthew J O'Connell, Jo MurrayJo MurrayThe Smc5/6 structural maintenance of chromosomes complex is required for efficient homologous recombination (HR). Defects in Smc5/6 result in chromosome missegregation and fragmentation. By characterising two Schizosaccharomyces pombe smc6 mutants, we define two separate functions for Smc5/6 in HR. The first represents the previously described defect in processing recombination-dependent DNA intermediates when replication forks collapse, which leads to increased rDNA recombination. The second novel function defines Smc5/6 as a positive regulator of recombination in the rDNA and correlates mechanistically with a requirement to load RPA and Rad52 onto chromatin genome-wide when replication forks are stably stalled by nucleotide depletion. Rad52 is required for all HR repair, but Rad52 loading in response to replication fork stalling is unexpected and does not correlate with damage-induced foci. We propose that Smc5/6 is required to maintain stalled forks in a stable recombination-competent conformation primed for replication restart.
History
Publication status
- Published
File Version
- Submitted version
Journal
EMBO JournalISSN
0261-4189Publisher
Nature Publishing GroupExternal DOI
Issue
2Volume
28Page range
144-155Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Notes
On Endnotes Ref: GDSC271Full text available
- Yes
Peer reviewed?
- Yes