DDK Phosphorylates checkpoint clamp component Rad9 and promotes its release from damaged chromatin

Furuya, Kanji, Miyabe, Izumi, Tsutsui, Yasuhiro, Paderi, Francesca, Kakusho, Naoko, Masai, Hisao, Niki, Hironori and Carr, Antony M (2010) DDK Phosphorylates checkpoint clamp component Rad9 and promotes its release from damaged chromatin. Molecular Cell, 40 (4). pp. 606-618. ISSN 1097-2765

Full text not available from this repository.

Abstract

When inappropriate DNA structures arise, they are sensed by DNA structure-dependent checkpoint pathways and subsequently repaired. Recruitment of checkpoint proteins to such structures precedes recruitment of proteins involved in DNA metabolism. Thus, checkpoints can regulate DNA metabolism. We show that fission yeast Rad9, a 9-1-1 heterotrimeric checkpoint-clamp component, is phosphorylated by Hsk1(Cdc7), the Schizosaccharomyces pombe Dbf4-dependent kinase (DDK) homolog, in response to replication-induced DNA damage. Phosphorylation of Rad9 disrupts its interaction with replication protein A (RPA) and is dependent on 9-1-1 chromatin loading, the Rad9-associated protein Rad4/Cut5(TopBP1), and prior phosphorylation by Rad3(ATR). rad9 mutants defective in DDK phosphorylation show wild-type checkpoint responses but abnormal DNA repair protein foci and decreased viability after replication stress. We propose that Rad9 phosphorylation by DDK releases Rad9 from DNA damage sites to facilitate DNA repair.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Depositing User: Izumi Miyabe
Date Deposited: 06 Feb 2012 20:51
Last Modified: 19 Jun 2013 09:44
URI: http://srodev.sussex.ac.uk/id/eprint/28437
📧 Request an update