8b4k | pdb_00008b4k

Rfa1-N-terminal domain in complex with phosphorylated Ddc2

spinqualitylabelsall models 8b4k, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8b4k is a 3 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RFA1_YEAST Binds to single-stranded sequences participating in DNA replication in addition to those mediating transcriptional repression (URS1) and activation (CAR1). Stimulates the activity of a cognate strand exchange protein (SEP1). It cooperates with T-AG and DNA topoisomerase I to unwind template DNA containing the simian virus 40 origin of DNA replication. Publication Abstract from PubMed The cell cycle checkpoint kinase Mec1(ATR) and its integral partner Ddc2(ATRIP) are vital for the DNA damage and replication stress response. Mec1-Ddc2 "senses" single-stranded DNA (ssDNA) by being recruited to the ssDNA binding Replication Protein A (RPA) via Ddc2. In this study, we show that a DNA damage-induced phosphorylation circuit modulates checkpoint recruitment and function. We demonstrate that Ddc2-RPA interactions modulate the association between RPA and ssDNA and that Rfa1-phosphorylation aids in the further recruitment of Mec1-Ddc2. We also uncover an underappreciated role for Ddc2 phosphorylation that enhances its recruitment to RPA-ssDNA that is important for the DNA damage checkpoint in yeast. The crystal structure of a phosphorylated Ddc2 peptide in complex with its RPA interaction domain provides molecular details of how checkpoint recruitment is enhanced, which involves Zn(2+). Using electron microscopy and structural modeling approaches, we propose that Mec1-Ddc2 complexes can form higher order assemblies with RPA when Ddc2 is phosphorylated. Together, our results provide insight into Mec1 recruitment and suggest that formation of supramolecular complexes of RPA and Mec1-Ddc2, modulated by phosphorylation, would allow for rapid clustering of damage foci to promote checkpoint signaling. A DNA damage-induced phosphorylation circuit enhances Mec1(ATR) Ddc2(ATRIP) recruitment to Replication Protein A.,Yates LA, Tannous EA, Morgan RM, Burgers PM, Zhang X Proc Natl Acad Sci U S A. 2023 Apr 4;120(14):e2300150120. doi: , 10.1073/pnas.2300150120. Epub 2023 Mar 30. PMID:36996117 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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