4BU0

Crystal structure of Rad4 BRCT1,2 in complex with a Crb2 phosphopeptide

Summary for 4BU0

• Entry DOI: 10.2210/pdb4bu0/pdb
• Related: 4BU1
• Descriptor: S-M CHECKPOINT CONTROL PROTEIN RAD4, DNA REPAIR PROTEIN RHP9, GLYCEROL, ... (5 entities in total)
• Functional Keywords: replication, topbp1, dna damage checkpoint
• Biological source: SCHIZOSACCHAROMYCES POMBE (FISSION YEAST); More
• Cellular location: Nucleus: P32372 P87074
• Total number of polymer chains: 3
• Total formula weight: 25155.53

Authors

Qu, M.,Rappas, M.,Wardlaw, C.P.,Garcia, V.,Carr, A.M.,Oliver, A.W.,Du, L.L.,Pearl, L.H. (deposition date: 2013-06-19, release date: 2013-10-09, Last modification date: 2024-10-23)

Primary citation

Qu, M.,Rappas, M.,Wardlaw, C.P.,Garcia, V.,Ren, J.Y.,Day, M.,Carr, A.M.,Oliver, A.W.,Du, L.L.,Pearl, L.H.
Phosphorylation-Dependent Assembly and Coordination of the DNA Damage Checkpoint Apparatus by Rad4(Topbp1.).
Mol.Cell, 51:723-, 2013

PubMed Abstract: The 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.

PubMed: 24074952
DOI: 10.1016/J.MOLCEL.2013.08.030

Experimental method

X-RAY DIFFRACTION (1.5 Å)