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| | ==Mre11 ATLD17/18 mutation retains Tel1/ATM activity but blocks DNA double-strand break repair== | | ==Mre11 ATLD17/18 mutation retains Tel1/ATM activity but blocks DNA double-strand break repair== |
| - | <StructureSection load='4hd0' size='340' side='right' caption='[[4hd0]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4hd0' size='340' side='right'caption='[[4hd0]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hd0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Pyrfu Pyrfu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HD0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HD0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hd0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_furiosus_DSM_3638 Pyrococcus furiosus DSM 3638]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HD0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HD0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mre11, PF1166 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=186497 PYRFU])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hd0 OCA], [http://pdbe.org/4hd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hd0 RCSB], [http://www.ebi.ac.uk/pdbsum/4hd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hd0 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=4hd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hd0 OCA], [https://pdbe.org/4hd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hd0 RCSB], [https://www.ebi.ac.uk/pdbsum/4hd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hd0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MRE11_PYRFU MRE11_PYRFU]] Involved in DNA double-strand break repair (DSBR). The Rad50/Mre11 complex possesses single-strand endonuclease activity and ATP-dependent double-strand-specific 3'-5' exonuclease activity. | + | [https://www.uniprot.org/uniprot/MRE11_PYRFU MRE11_PYRFU] Involved in DNA double-strand break repair (DSBR). The Rad50/Mre11 complex possesses single-strand endonuclease activity and ATP-dependent double-strand-specific 3'-5' exonuclease activity. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | The Mre11 complex (Mre11-Rad50-Nbs1 or MRN) binds double-strand breaks where it interacts with CtIP/Ctp1/Sae2 and ATM/Tel1 to preserve genome stability through its functions in homology-directed repair, checkpoint signaling and telomere maintenance. Here, we combine biochemical, structural and in vivo functional studies to uncover key properties of Mre11-W243R, a mutation identified in two pediatric cancer patients with enhanced ataxia telangiectasia-like disorder. Purified human Mre11-W243R retains nuclease and DNA binding activities in vitro. X-ray crystallography of Pyrococcus furiosus Mre11 indicates that an analogous mutation leaves the overall Mre11 three-dimensional structure and nuclease sites intact but disorders surface loops expected to regulate DNA and Rad50 interactions. The equivalent W248R allele in fission yeast allows Mre11 to form an MRN complex that efficiently binds double-strand breaks, activates Tel1/ATM and maintains telomeres; yet, it causes hypersensitivity to ionizing radiation and collapsed replication forks, increased Rad52 foci, defective Chk1 signaling and meiotic failure. W248R differs from other ataxia telangiectasia-like disorder analog alleles by the reduced stability of its interaction with Rad50 in cell lysates. Collective results suggest a separation-of-function mutation that disturbs interactions amongst the MRN subunits and Ctp1 required for DNA end processing in vivo but maintains interactions sufficient for Tel1/ATM checkpoint and telomere maintenance functions.
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| - | Mre11 ATLD17/18 mutation retains Tel1/ATM activity but blocks DNA double-strand break repair.,Limbo O, Moiani D, Kertokalio A, Wyman C, Tainer JA, Russell P Nucleic Acids Res. 2012 Dec 1;40(22):11435-11449. Epub 2012 Oct 17. PMID:23080121<ref>PMID:23080121</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4hd0" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pyrfu]] | + | [[Category: Large Structures]] |
| - | [[Category: Kertokalio, A]] | + | [[Category: Pyrococcus furiosus DSM 3638]] |
| - | [[Category: Limbo, O]] | + | [[Category: Kertokalio A]] |
| - | [[Category: Moiani, D]] | + | [[Category: Limbo O]] |
| - | [[Category: Russell, P]] | + | [[Category: Moiani D]] |
| - | [[Category: Tainer, J A]] | + | [[Category: Russell P]] |
| - | [[Category: Wyman, C]] | + | [[Category: Tainer JA]] |
| - | [[Category: Dna binding protein]]
| + | [[Category: Wyman C]] |
| - | [[Category: Double-strand break repair]]
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| - | [[Category: Mutation l204r]]
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| - | [[Category: Nbs1]]
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| - | [[Category: Nuclease enzyme]]
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| - | [[Category: Rad50]]
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