4o4k: Difference between revisions
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New page: '''Unreleased structure''' The entry 4o4k is ON HOLD Authors: Shibata, A. , Moiani, D. , Arvai, A.S. , Perry, J. , Harding, S.M. , Genois, M. , Maity, R. , Rossum-Fikkert, S. , Kertokal... |
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==DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities== | |||
<StructureSection load='4o4k' size='340' side='right'caption='[[4o4k]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4o4k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermotoga_maritima_MSB8 Thermotoga maritima MSB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O4K 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]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PK:2-AMINO-5-(4-HYDROXYBENZYL)-4H-1LAMBDA~4~,3-THIAZOL-4-ONE'>2PK</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=4o4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o4k OCA], [https://pdbe.org/4o4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o4k RCSB], [https://www.ebi.ac.uk/pdbsum/4o4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o4k ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9X1X0_THEMA Q9X1X0_THEMA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
MRE11 within the MRE11-RAD50-NBS1 (MRN) complex acts in DNA double-strand break repair (DSBR), detection, and signaling; yet, how its endo- and exonuclease activities regulate DSBR by nonhomologous end-joining (NHEJ) versus homologous recombination (HR) remains enigmatic. Here, we employed structure-based design with a focused chemical library to discover specific MRE11 endo- or exonuclease inhibitors. With these inhibitors, we examined repair pathway choice at DSBs generated in G2 following radiation exposure. While nuclease inhibition impairs radiation-induced replication protein A (RPA) chromatin binding, suggesting diminished resection, the inhibitors surprisingly direct different repair outcomes. Endonuclease inhibition promotes NHEJ in lieu of HR, while exonuclease inhibition confers a repair defect. Collectively, the results describe nuclease-specific MRE11 inhibitors, define distinct nuclease roles in DSB repair, and support a mechanism whereby MRE11 endonuclease initiates resection, thereby licensing HR followed by MRE11 exonuclease and EXO1/BLM bidirectional resection toward and away from the DNA end, which commits to HR. | |||
DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities.,Shibata A, Moiani D, Arvai AS, Perry J, Harding SM, Genois MM, Maity R, van Rossum-Fikkert S, Kertokalio A, Romoli F, Ismail A, Ismalaj E, Petricci E, Neale MJ, Bristow RG, Masson JY, Wyman C, Jeggo PA, Tainer JA Mol Cell. 2013 Dec 3. pii: S1097-2765(13)00828-9. doi:, 10.1016/j.molcel.2013.11.003. PMID:24316220<ref>PMID:24316220</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4o4k" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Thermotoga maritima MSB8]] | |||
[[Category: Arvai AS]] | |||
[[Category: Bristow RG]] | |||
[[Category: Genois M]] | |||
[[Category: Harding SM]] | |||
[[Category: Ismail A]] | |||
[[Category: Ismalaj E]] | |||
[[Category: Jeggo PA]] | |||
[[Category: Kertokalio A]] | |||
[[Category: Maity R]] | |||
[[Category: Masson J]] | |||
[[Category: Moiani D]] | |||
[[Category: Neale MJ]] | |||
[[Category: Perry J]] | |||
[[Category: Petricci E]] | |||
[[Category: Romoli F]] | |||
[[Category: Rossum-Fikkert S]] | |||
[[Category: Shibata A]] | |||
[[Category: Tainer JA]] | |||
[[Category: Wyman C]] | |||
Latest revision as of 17:07, 20 September 2023
DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities
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