7st9
From Proteopedia
Open state of Rad24-RFC:9-1-1 bound to a 5' ss/dsDNA junction
Structural highlights
FunctionRAD24_YEAST Participates in checkpoint pathways arrest of the cell cycle, a mechanism that allows the DNA repair pathways to act to restore the integrity of the DNA prior to DNA synthesis or separation of the replicated chromosomes. Regulates the DNA damage checkpoint pathway throughout the cell cycle, when associated with RCF5. Component of the RFC-like RAD24-RFC complex which loads the checkpoint clamp DDC1:MEC3:RAD17 complex and is involved in DNA repair pathways. During a clamp loading circle, the RFC:clamp complex binds to DNA and the recognition of the double-stranded/single-stranded junction stimulates ATP hydrolysis by RFC. The complex presumably provides bipartite ATP sites in which one subunit supplies a catalytic site for hydrolysis of ATP bound to the neighboring subunit. Dissociation of RFC from the clamp leaves the clamp encircling DNA.[1] [2] [3] Publication Abstract from PubMedSingle-stranded or double-stranded DNA junctions with recessed 5' ends serve as loading sites for the checkpoint clamp, 9-1-1, which mediates activation of the apical checkpoint kinase, ATR(Mec1). However, the basis for 9-1-1's recruitment to 5' junctions is unclear. Here, we present structures of the yeast checkpoint clamp loader, Rad24-replication factor C (RFC), in complex with 9-1-1 and a 5' junction and in a post-ATP-hydrolysis state. Unexpectedly, 9-1-1 adopts both closed and planar open states in the presence of Rad24-RFC and DNA. Moreover, Rad24-RFC associates with the DNA junction in the opposite orientation of processivity clamp loaders with Rad24 exclusively coordinating the double-stranded region. ATP hydrolysis stimulates conformational changes in Rad24-RFC, leading to disengagement of DNA-loaded 9-1-1. Together, these structures explain 9-1-1's recruitment to 5' junctions and reveal new principles of sliding clamp loading. Mechanisms of loading and release of the 9-1-1 checkpoint clamp.,Castaneda JC, Schrecker M, Remus D, Hite RK Nat Struct Mol Biol. 2022 Apr;29(4):369-375. doi: 10.1038/s41594-022-00741-7. , Epub 2022 Mar 21. PMID:35314831[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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