3G65

Crystal structure of the rad9-rad1-hus1 DNA damage checkpoint complex--implications for clamp loading and regulation.

(2009) Mol Cell 34: 735-745

• PubMed: 19446481 Search on PubMed
• DOI: https://doi.org/10.1016/j.molcel.2009.04.027
• Primary Citation of Related Structures:  
  3G65


• PubMed 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(cip1/waf1).

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Organizational Affiliation: 

CR-UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, Chelsea, SW36JB London, UK.