View source for 4o24


==DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities==
<StructureSection load='4o24' size='340' side='right'caption='[[4o24]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4o24]] 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=4O24 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O24 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2Q0:5-(4-HYDROXYBENZYL)-3-(2-METHYLPROPYL)-2-THIOXO-2,3-DIHYDRO-4H-1LAMBDA~4~,3-THIAZOL-4-ONE'>2Q0</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=4o24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o24 OCA], [https://pdbe.org/4o24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o24 RCSB], [https://www.ebi.ac.uk/pdbsum/4o24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o24 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4o24" 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]]