Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1

Furuya, Kanji, Poitelea, Marius, Guo, Liandi, Caspari, Thomas and Carr, Antony M (2004) Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1. Genes and Development, 18. pp. 1154-1164. ISSN 0890-9369

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Abstract

To gain insight into the function and organization of proteins assembled on the DNA in response to genotoxic insult we investigated the phosphorylation of the Schizosaccharomyces pombe PCNA-like checkpoint protein Rad9. C-terminal T412/S423 phosphorylation of Rad9 by Rad3ATR occurs in S phase without replication stress. Rad3ATR and Tel1ATM phosphorylate these same residues, plus additional ones, in response to DNA damage. In S phase and after damage, only Rad9 phosphorylated on T412/S423, but not unphosphorylated Rad9, associates with a two-BRCT-domain region of the essential Rad4TOPBP1 protein. Rad9¿Rad4TOPBP1 interaction is required to activate the Chk1 damage checkpoint but not the Cds1 replication checkpoint. When the Rad9-T412/S423 are phosphorylated, Rad4TOPBP1 coprecipitates with Rad3ATR, suggesting that phosphorylation coordinates formation of an active checkpoint complex.

Item Type: Article
Additional Information: Senior Author, all authors from Sussex.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Antony Carr
Date Deposited: 06 Feb 2012 21:11
Last Modified: 20 Apr 2012 14:22
URI: http://sro.sussex.ac.uk/id/eprint/30058
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