View source for 6rml


==Crystal structure of TOPBP1 BRCT0,1,2 in complex with a 53BP1 phosphopeptide==
<StructureSection load='6rml' size='340' side='right'caption='[[6rml]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rml]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RML OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RML FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.81&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6rml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rml OCA], [https://pdbe.org/6rml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rml RCSB], [https://www.ebi.ac.uk/pdbsum/6rml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rml ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TOPB1_HUMAN TOPB1_HUMAN] Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double-stranded DNA breaks and nicks as well as single-stranded DNA. Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage. Induces a large increase in the kinase activity of ATR.<ref>PMID:10498869</ref> <ref>PMID:11395493</ref> <ref>PMID:11714696</ref> <ref>PMID:12697828</ref> <ref>PMID:15075294</ref> <ref>PMID:16530042</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Coordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ubiquitylation on other proteins, and are themselves carriers of such regulatory signals. Here we show that the DNA damage checkpoint regulating S-phase entry is controlled by a phosphorylation-dependent interaction of 53BP1 and TOPBP1. BRCT domains of TOPBP1 selectively bind conserved phosphorylation sites in the N-terminus of 53BP1. Mutation of these sites does not affect formation of 53BP1 or ATM foci following DNA damage, but abolishes recruitment of TOPBP1, ATR and CHK1 to 53BP1 damage foci, abrogating cell cycle arrest and permitting progression into S-phase. TOPBP1 interaction with 53BP1 is structurally complimentary to its interaction with RAD9-RAD1-HUS1, allowing these damage recognition factors to bind simultaneously to the same TOPBP1 molecule and cooperate in ATR activation in the G1 DNA damage checkpoint.

Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.,Bigot N, Day M, Baldock RA, Watts FZ, Oliver AW, Pearl LH Elife. 2019 May 28;8. pii: 44353. doi: 10.7554/eLife.44353. PMID:31135337<ref>PMID:31135337</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rml" style="background-color:#fffaf0;"></div>

==See Also==
*[[Topoisomerase binding protein|Topoisomerase binding protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Day M]]
[[Category: Oliver AW]]
[[Category: Pearl LH]]