Structural highlights
7st9 is a 10 chain structure with sequence from Saccharomyces cerevisiae and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | Electron Microscopy, Resolution 2.2Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
RAD24_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 PubMed
Single-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
- ↑ Naiki T, Shimomura T, Kondo T, Matsumoto K, Sugimoto K. Rfc5, in cooperation with rad24, controls DNA damage checkpoints throughout the cell cycle in Saccharomyces cerevisiae. Mol Cell Biol. 2000 Aug;20(16):5888-96. PMID:10913172
- ↑ Naiki T, Kondo T, Nakada D, Matsumoto K, Sugimoto K. Chl12 (Ctf18) forms a novel replication factor C-related complex and functions redundantly with Rad24 in the DNA replication checkpoint pathway. Mol Cell Biol. 2001 Sep;21(17):5838-45. PMID:11486023
- ↑ Majka J, Burgers PM. Yeast Rad17/Mec3/Ddc1: a sliding clamp for the DNA damage checkpoint. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2249-54. Epub 2003 Feb 25. PMID:12604797 doi:http://dx.doi.org/10.1073/pnas.0437148100
- ↑ Castaneda JC, Schrecker M, Remus D, Hite RK. Mechanisms of loading and release of the 9-1-1 checkpoint clamp. Nat Struct Mol Biol. 2022 Apr;29(4):369-375. PMID:35314831 doi:10.1038/s41594-022-00741-7
