7Z6H

Structure of DNA-bound human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp

Summary for 7Z6H

• Entry DOI: 10.2210/pdb7z6h/pdb
• EMDB information: 14527
• Descriptor: Cell cycle checkpoint control protein RAD9A, Cell cycle checkpoint protein RAD1,Cell cycle checkpoint protein RAD17, Checkpoint protein HUS1, ... (9 entities in total)
• Functional Keywords: dna damage checkpoint, rad17-rfc, 9-1-1, dna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 516747.73

Authors

Day, M.,Oliver, A.W.,Pearl, L.H. (deposition date: 2022-03-11, release date: 2022-05-04, Last modification date: 2022-08-31)

Primary citation

Day, M.,Oliver, A.W.,Pearl, L.H.
Structure of the human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp bound to a dsDNA-ssDNA junction.
Nucleic Acids Res., 50:8279-8289, 2022

PubMed Abstract: The RAD9-RAD1-HUS1 (9-1-1) clamp forms one half of the DNA damage checkpoint system that signals the presence of substantial regions of single-stranded DNA arising from replication fork collapse or resection of DNA double strand breaks. Loaded at the 5'-recessed end of a dsDNA-ssDNA junction by the RAD17-RFC clamp loader complex, the phosphorylated C-terminal tail of the RAD9 subunit of 9-1-1 engages with the mediator scaffold TOPBP1 which in turn activates the ATR kinase, localised through the interaction of its constitutive partner ATRIP with RPA-coated ssDNA. Using cryogenic electron microscopy (cryoEM) we have determined the structure of a complex of the human RAD17-RFC clamp loader bound to human 9-1-1, engaged with a dsDNA-ssDNA junction. The structure answers the key questions of how RAD17 confers specificity for 9-1-1 over PCNA, and how the clamp loader specifically recognises the recessed 5' DNA end and fixes the orientation of 9-1-1 on the ssDNA.

PubMed: 35819203
DOI: 10.1093/nar/gkac588

Experimental method

ELECTRON MICROSCOPY (3.59 Å)