Summary information and primary citation
- PDB-id
- 7z6h; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- DNA binding protein
- Method
- cryo-EM (3.59 Å)
- Summary
- Structure of DNA-bound human rad17-rfc clamp loader and 9-1-1 checkpoint clamp
- Reference
- Day M, Oliver AW, Pearl LH (2022): "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. doi: 10.1093/nar/gkac588.
- 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.
