Cancer Institute A national cancer institute
designated cancer center

Teresa Wang

Publication Details

  • Rad3-dependent phosphorylation of the checkpoint clamp regulates repair-pathway choice NATURE CELL BIOLOGY Kai, M., Furuya, K., Paderi, F., Carr, A. M., Wang, T. S. 2007; 9 (6): 691-U148


    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.

    View details for DOI 10.1038/ncb1600

    View details for Web of Science ID 000246922700015

    View details for PubMedID 17515930

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