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4bu1

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Revision as of 07:23, 24 December 2014

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

Structural highlights

4bu1 is a 4 chain structure with sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
NonStd Res:
Related:	4bu0
Resources:	FirstGlance, OCA, RCSB, PDBsum

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 PubMed

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.

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

↑ Willson J, Wilson S, Warr N, Watts FZ. Isolation and characterization of the Schizosaccharomyces pombe rhp9 gene: a gene required for the DNA damage checkpoint but not the replication checkpoint. Nucleic Acids Res. 1997 Jun 1;25(11):2138-46. PMID:9153313
↑ Saka Y, Esashi F, Matsusaka T, Mochida S, Yanagida M. Damage and replication checkpoint control in fission yeast is ensured by interactions of Crb2, a protein with BRCT motif, with Cut5 and Chk1. Genes Dev. 1997 Dec 15;11(24):3387-400. PMID:9407031
↑ Sanders SL, Portoso M, Mata J, Bahler J, Allshire RC, Kouzarides T. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell. 2004 Nov 24;119(5):603-14. PMID:15550243 doi:http://dx.doi.org/10.1016/j.cell.2004.11.009
↑ Qu M, Rappas M, Wardlaw CP, Garcia V, Ren JY, Day M, Carr AM, Oliver AW, Du LL, Pearl LH. Phosphorylation-Dependent Assembly and Coordination of the DNA Damage Checkpoint Apparatus by Rad4(TopBP1.). Mol Cell. 2013 Sep 26;51(6):723-36. doi: 10.1016/j.molcel.2013.08.030. PMID:24074952 doi:http://dx.doi.org/10.1016/j.molcel.2013.08.030

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bu1"

@@ Line 8: / Line 8: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bu1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bu1 RCSB], [http://www.ebi.ac.uk/pdbsum/4bu1 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/RAD4_SCHPO 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. [[http://www.uniprot.org/uniprot/RHP9_SCHPO 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.<ref>PMID:9153313</ref> <ref>PMID:9407031</ref> <ref>PMID:15550243</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4bu1

From Proteopedia

Revision as of 07:23, 24 December 2014

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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