3G65

Crystal Structure of the Human Rad9-Rad1-Hus1 DNA Damage Checkpoint Complex

Summary for 3G65

• Entry DOI: 10.2210/pdb3g65/pdb
• Descriptor: Cell cycle checkpoint control protein RAD9A, Cell cycle checkpoint protein RAD1, Checkpoint protein HUS1, ... (4 entities in total)
• Functional Keywords: pcna, dna binding clamp, dna damage, dna repair, exonuclease, hydrolase, nuclease, nucleus, phosphoprotein, cell cycle
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q99638 O60671 O60921
• Total number of polymer chains: 3
• Total formula weight: 96038.32

Authors

Dore, A.S.,Kilkenny, M.L.,Rzechorzek, N.J.,Pearl, L.H. (deposition date: 2009-02-06, release date: 2009-05-26, Last modification date: 2023-09-06)

Primary citation

Dore, A.S.,Kilkenny, M.L.,Rzechorzek, N.J.,Pearl, L.H.
Crystal structure of the rad9-rad1-hus1 DNA damage checkpoint complex--implications for clamp loading and regulation.
Mol.Cell, 34:735-745, 2009

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).

PubMed: 19446481
DOI: 10.1016/j.molcel.2009.04.027

Experimental method

X-RAY DIFFRACTION (2.9 Å)