4bu0
From Proteopedia
Crystal structure of Rad4 BRCT1,2 in complex with a Crb2 phosphopeptide
Structural highlights
Function[RAD4_SCHPO] Essential component for DNA replication and also the checkpoint control system which couples S and M phases. May directly or indirectly interact with chromatin proteins to form the complex required for the initiation and/or progression of DNA synthesis. [RHP9_SCHPO] Essential for cell cycle arrest at the G1 and G2 stages following DNA damage by X-, and UV-irradiation, or inactivation of DNA ligase. Plays a role in the response to DNA damage.[1] [2] [3] Publication Abstract from PubMedThe BRCT-domain protein Rad4(TopBP1) facilitates activation of the DNA damage checkpoint in Schizosaccharomyces pombe by physically coupling the Rad9-Rad1-Hus1 clamp, the Rad3(ATR) -Rad26(ATRIP) kinase complex, and the Crb2(53BP1) mediator. We have now determined crystal structures of the BRCT repeats of Rad4(TopBP1), revealing a distinctive domain architecture, and characterized their phosphorylation-dependent interactions with Rad9 and Crb2(53BP1). We identify a cluster of phosphorylation sites in the N-terminal region of Crb2(53BP1) that mediate interaction with Rad4(TopBP1) and reveal a hierarchical phosphorylation mechanism in which phosphorylation of Crb2(53BP1) residues Thr215 and Thr235 promotes phosphorylation of the noncanonical Thr187 site by scaffolding cyclin-dependent kinase (CDK) recruitment. Finally, we show that the simultaneous interaction of a single Rad4(TopBP1) molecule with both Thr187 phosphorylation sites in a Crb2(53BP1) dimer is essential for establishing the DNA damage checkpoint. Phosphorylation-Dependent Assembly and Coordination of the DNA Damage Checkpoint Apparatus by Rad4(TopBP1.).,Qu M, Rappas M, Wardlaw CP, Garcia V, Ren JY, Day M, Carr AM, Oliver AW, Du LL, Pearl LH Mol Cell. 2013 Sep 26;51(6):723-36. doi: 10.1016/j.molcel.2013.08.030. PMID:24074952[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Cbs 356 | Carr, A M | Du, L L | Garcia, V | Oliver, A W | Pearl, L H | Qu, M | Rappas, M | Wardlaw, C P | Dna damage checkpoint | Replication | Topbp1
