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{{STRUCTURE_4o4k|  PDB=4o4k  |  SCENE=  }}
==DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities==
===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]] 2.10&Aring;' scene=''>
{{ABSTRACT_PUBMED_24316220}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4o4k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Thema Thema]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O4K FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nzv|4nzv]], [[4o43|4o43]], [[4o24|4o24]], [[4o5g|4o5g]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TM_1635 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243274 THEMA])</td></tr>
<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=4o4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o4k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o4k RCSB], [http://www.ebi.ac.uk/pdbsum/4o4k PDBsum]</span></td></tr>
</table>
<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.


==About this Structure==
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>
[[4o4k]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O4K OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
<ref group="xtra">PMID:024316220</ref><references group="xtra"/><references/>
</div>
[[Category: Arvai, A S.]]
== References ==
[[Category: Bristow, R G.]]
<references/>
[[Category: Genois, M.]]
__TOC__
[[Category: Harding, S M.]]
</StructureSection>
[[Category: Ismail, A.]]
[[Category: Thema]]
[[Category: Ismalaj, E.]]
[[Category: Arvai, A S]]
[[Category: Jeggo, P A.]]
[[Category: Bristow, R G]]
[[Category: Kertokalio, A.]]
[[Category: Genois, M]]
[[Category: Maity, R.]]
[[Category: Harding, S M]]
[[Category: Masson, J.]]
[[Category: Ismail, A]]
[[Category: Moiani, D.]]
[[Category: Ismalaj, E]]
[[Category: Neale, M J.]]
[[Category: Jeggo, P A]]
[[Category: Perry, J.]]
[[Category: Kertokalio, A]]
[[Category: Petricci, E.]]
[[Category: Maity, R]]
[[Category: Romoli, F.]]
[[Category: Masson, J]]
[[Category: Rossum-Fikkert, S.]]
[[Category: Moiani, D]]
[[Category: Shibata, A.]]
[[Category: Neale, M J]]
[[Category: Tainer, J A.]]
[[Category: Perry, J]]
[[Category: Wyman, C.]]
[[Category: Petricci, E]]
[[Category: Romoli, F]]
[[Category: Rossum-Fikkert, S]]
[[Category: Shibata, A]]
[[Category: Tainer, J A]]
[[Category: Wyman, C]]
[[Category: Dna binding protein-inhibitor complex]]
[[Category: Dna binding protein-inhibitor complex]]
[[Category: Dna repair dna double-strand break repair]]
[[Category: Dna repair dna double-strand break repair]]
[[Category: Dna repair dna double-strand break repair thermophilic mre11]]
[[Category: Dna repair dna double-strand break repair thermophilic mre11]]
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