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-Structure paper
Title | Structure of the human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp bound to a dsDNA-ssDNA junction. |
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Journal, issue, pages | Nucleic Acids Res, Vol. 50, Issue 14, Page 8279-8289, Year 2022 |
Publish date | Aug 12, 2022 |
Authors | Matthew Day / Antony W Oliver / Laurence H Pearl / |
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 ...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. |
External links | Nucleic Acids Res / PubMed:35819203 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.59 Å |
Structure data | EMDB-14527, PDB-7z6h: |
Chemicals | ChemComp-AGS: |
Source |
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Keywords | DNA BINDING PROTEIN / DNA damage checkpoint / Rad17-RFC / 9-1-1 |