4o24: Difference between revisions

Revision as of 08:52, 18 January 2023

DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities

Structural highlights

4o24 is a 2 chain structure with sequence from Thermotoga maritima MSB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	2Q0, MN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q9X1X0_THEMA

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities. Mol Cell. 2013 Dec 3. pii: S1097-2765(13)00828-9. doi:, 10.1016/j.molcel.2013.11.003. PMID:24316220 doi:https://dx.doi.org/10.1016/j.molcel.2013.11.003

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OCA

[1] 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. DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities. Mol Cell. 2013 Dec 3. pii: S1097-2765(13)00828-9. doi:, 10.1016/j.molcel.2013.11.003. PMID:24316220 doi:https://dx.doi.org/10.1016/j.molcel.2013.11.003

[1]

@@ Line 3: / Line 3: @@
 <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 [http://en.wikipedia.org/wiki/Thema Thema]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O24 FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
+</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nzv|4nzv]], [[4o43|4o43]], [[4o4k|4o4k]], [[4o5g|4o5g]]</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>
-<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=4o24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o24 OCA], [http://pdbe.org/4o24 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o24 RCSB], [http://www.ebi.ac.uk/pdbsum/4o24 PDBsum], [http://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 ==
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Thema]]
+[[Category: Thermotoga maritima MSB8]]
-[[Category: Arvai, A S]]
+[[Category: Arvai AS]]
-[[Category: Bristow, R G]]
+[[Category: Bristow RG]]
-[[Category: Genois, M]]
+[[Category: Genois M]]
-[[Category: Harding, S M]]
+[[Category: Harding SM]]
-[[Category: Ismail, A]]
+[[Category: Ismail A]]
-[[Category: Ismalaj, E]]
+[[Category: Ismalaj E]]
-[[Category: Jeggo, P A]]
+[[Category: Jeggo PA]]
-[[Category: Kertokalio, A]]
+[[Category: Kertokalio A]]
-[[Category: Maity, R]]
+[[Category: Maity R]]
-[[Category: Masson, J]]
+[[Category: Masson J]]
-[[Category: Moiani, D]]
+[[Category: Moiani D]]
-[[Category: Neale, M J]]
+[[Category: Neale MJ]]
-[[Category: Perry, J]]
+[[Category: Perry J]]
-[[Category: Petricci, E]]
+[[Category: Petricci E]]
-[[Category: Romoli, F]]
+[[Category: Romoli F]]
-[[Category: Rossum-Fikkert, S]]
+[[Category: Rossum-Fikkert S]]
-[[Category: Shibata, A]]
+[[Category: Shibata A]]
-[[Category: Tainer, J A]]
+[[Category: Tainer JA]]
-[[Category: Wyman, C]]
+[[Category: Wyman C]]
-[[Category: Dna binding protein-inhibitor complex]]
-[[Category: Dna repair dna double-strand break repair]]
-[[Category: Dna repair dna double-strand break repair thermophilic mre11 nuclease]]

4o24: Difference between revisions

Revision as of 08:52, 18 January 2023

DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities

Structural highlights

Function

Publication Abstract from PubMed

References

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