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

Kai, Mihoko, Furuya, Kanji, Paderi, Francesca, Carr, Antony M and Wang, Teresa S F (2007) Rad3-dependent phosphorylation of the checkpoint clamp regulates repair-pathway choice. Nature: Cell Biology, 9 (6). pp. 691-697. ISSN 1465-7392

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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 rad9T225C 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Francesca Paderi
Date Deposited: 06 Feb 2012 19:58
Last Modified: 07 Aug 2012 07:42
URI: http://sro.sussex.ac.uk/id/eprint/23329
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