Crystal Structure of the Rad9-Rad1-Hus1 DNA Damage Checkpoint Complex¿Implications for Clamp Loading and Regulation

Doré, Andrew S, Kilkenny, Mairi L, Rzechorzek, Neil J and Pearl, Laurence H (2009) Crystal Structure of the Rad9-Rad1-Hus1 DNA Damage Checkpoint Complex¿Implications for Clamp Loading and Regulation. Molecular Cell, 34 (6). pp. 735-745. ISSN 1097-2765

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Abstract

Rad9, Rad1, and Hus1 form a heterotrimeric complex (9-1-1) that is loaded onto DNA at sites of DNA damage. DNA-loaded 9-1-1 activates signaling through the Chk1 arm of the DNA damage checkpoint response via recruitment and stimulation of ATR. Additionally, 9-1-1 may play a direct role in facilitating DNA damage repair via interaction with a number of DNA repair enzymes. We have now determined the crystal structure of the human 9-1-1 complex, revealing a toroidal structure with a similar architecture to the homotrimeric PCNA DNA-binding clamp. The structure explains the formation of a unique heterotrimeric arrangement and reveals significant differences among the three subunits in the sites implicated in binding to the clamp loader and to ligand proteins. Biochemical analysis reveals a single repair enzyme-binding site on 9-1-1 that can be blocked competitively by the PCNA-binding cell-cycle regulator p21

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Depositing User: Laurence Pearl
Date Deposited: 06 Feb 2012 18:15
Last Modified: 08 Oct 2012 10:58
URI: http://sro.sussex.ac.uk/id/eprint/15428
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