Rad3-dependent phosphorylation of the checkpoint clamp regulates repair-pathway choice.

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.
Mesh Terms:
Cell Cycle, Cell Cycle Proteins, DNA Damage, DNA Repair, Gene Expression Regulation, Fungal, Genes, cdc, Genomic Instability, Phosphorylation, Protein Kinases, Saccharomyces cerevisiae, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Signal Transduction, Threonine, Ubiquitin-Conjugating Enzymes
Nat. Cell Biol.
Date: Jun. 01, 2007
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