4nzv
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4nzv]] 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=4NZV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NZV FirstGlance]. <br> | <table><tr><td colspan='2'>[[4nzv]] 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=4NZV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NZV FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.901Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=4nzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nzv OCA], [https://pdbe.org/4nzv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nzv RCSB], [https://www.ebi.ac.uk/pdbsum/4nzv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nzv ProSAT]</span></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=4nzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nzv OCA], [https://pdbe.org/4nzv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nzv RCSB], [https://www.ebi.ac.uk/pdbsum/4nzv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nzv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/Q9X1X0_THEMA Q9X1X0_THEMA] | [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. | ||
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| - | 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> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4nzv" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities
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Categories: Large Structures | Thermotoga maritima MSB8 | Arvai AS | Bristow RG | Genois M | Harding SM | Ismail A | Ismalaj E | Jeggo PA | Kertokalio A | Maity R | Masson J | Moiani D | Neale MJ | Perry J | Petricci E | Romoli F | Rossum-Fikkert S | Shibata A | Tainer JA | Wyman C
