Reference - PMID:17515930 - Rad3-dependent phosphorylation of the checkpoint clamp regulates repair-pathway choice.
Reference summary
- PubMed ID
- PMID:17515930
- Title
- Rad3-dependent phosphorylation of the checkpoint clamp regulates repair-pathway choice.
- Authors
- Kai M, Furuya K, Paderi F, Carr AM, Wang TS
- Citation
- Nat Cell Biol 2007 Jun;9(6):691-7
- Publication year
- 2007
- Abstract
- When replication forks collapse, Rad3 phosphorylates the checkpoint-clamp protein Rad9 in a manner that depends on Thr 225, a residue within the PCNA-like domain. The physiological function of Thr 225-dependent Rad9 phosphorylation, however, remains elusive. Here, we show that Thr 225-dependent Rad9 phosphorylation by Rad3 regulates DNA repair pathways. A rad9(T225C) mutant induces a translesion synthesis (TLS)-dependent high spontaneous mutation rate and a hyper-recombination phenotype. Consistent with this, Rad9 coprecipitates with the post-replication repair protein Mms2. This interaction is dependent on Rad9 Thr 225 and is enhanced by DNA damage. Genetic analyses indicate that Thr 225-dependent Rad9 phosphorylation prevents inappropriate Rhp51-dependent recombination, potentially by redirecting the repair through a Pli1-mediated sumoylation pathway into the error-free branch of the Rhp6 repair pathway. Our findings reveal a new mechanism by which phosphorylation of Rad9 at Thr 225 regulates the choice of repair pathways for maintaining genomic integrity during the cell cycle.
