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| | ==Eukaryotic Rad50 Functions as A Rod-shaped Dimer== | | ==Eukaryotic Rad50 Functions as A Rod-shaped Dimer== |
| - | <StructureSection load='5gox' size='340' side='right' caption='[[5gox]], [[Resolution|resolution]] 2.41Å' scene=''> | + | <StructureSection load='5gox' size='340' side='right'caption='[[5gox]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5gox]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GOX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GOX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5gox]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GOX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GOX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.405Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5gox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gox OCA], [http://pdbe.org/5gox PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gox RCSB], [http://www.ebi.ac.uk/pdbsum/5gox PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gox 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=5gox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gox OCA], [https://pdbe.org/5gox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gox RCSB], [https://www.ebi.ac.uk/pdbsum/5gox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gox ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/RAD50_HUMAN RAD50_HUMAN]] Nijmegen breakage syndrome-like disorder;Hereditary breast and ovarian cancer syndrome. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/RAD50_HUMAN RAD50_HUMAN] Nijmegen breakage syndrome-like disorder;Hereditary breast and ovarian cancer syndrome. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RAD50_HUMAN RAD50_HUMAN]] Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11A to prevent nucleolytic degradation past a given point (PubMed:11741547, PubMed:9590181, PubMed:9705271, PubMed:9651580). The complex may also be required for DNA damage signaling via activation of the ATM kinase (PubMed:15064416). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888).<ref>PMID:10888888</ref> <ref>PMID:11741547</ref> <ref>PMID:15064416</ref> <ref>PMID:9590181</ref> <ref>PMID:9651580</ref> <ref>PMID:9705271</ref> | + | [https://www.uniprot.org/uniprot/RAD50_HUMAN RAD50_HUMAN] Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11A to prevent nucleolytic degradation past a given point (PubMed:11741547, PubMed:9590181, PubMed:9705271, PubMed:9651580). The complex may also be required for DNA damage signaling via activation of the ATM kinase (PubMed:15064416). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888).<ref>PMID:10888888</ref> <ref>PMID:11741547</ref> <ref>PMID:15064416</ref> <ref>PMID:9590181</ref> <ref>PMID:9651580</ref> <ref>PMID:9705271</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The Rad50 hook interface is crucial for assembly and various functions of the Mre11 complex. Previous analyses suggested that Rad50 molecules interact within (intracomplex) or between (intercomplex) dimeric complexes. In this study, we determined the structure of the human Rad50 hook and coiled-coil domains. The data suggest that the predominant structure is the intracomplex, in which the two parallel coiled coils proximal to the hook form a rod shape, and that a novel interface within the coiled-coil domains of Rad50 stabilizes the interaction of Rad50 protomers in the dimeric assembly. In yeast, removal of the coiled-coil interface compromised Tel1 activation without affecting DNA repair, while simultaneous disruption of that interface and the hook phenocopied a null mutation. The results demonstrate that the hook and coiled-coil interfaces coordinately promote intracomplex assembly and define the intracomplex as the functional form of the Mre11 complex. |
| | + | |
| | + | Eukaryotic Rad50 functions as a rod-shaped dimer.,Park YB, Hohl M, Padjasek M, Jeong E, Jin KS, Krezel A, Petrini JH, Cho Y Nat Struct Mol Biol. 2017 Mar;24(3):248-257. doi: 10.1038/nsmb.3369. Epub 2017, Jan 30. PMID:28134932<ref>PMID:28134932</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 5gox" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cho, Y]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Hohl, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Jeong, E]] | + | [[Category: Cho Y]] |
| - | [[Category: Jin, K S]] | + | [[Category: Hohl M]] |
| - | [[Category: Krezel, A]] | + | [[Category: Jeong E]] |
| - | [[Category: Padjasek, M]] | + | [[Category: Jin KS]] |
| - | [[Category: Park, Y B]] | + | [[Category: Krezel A]] |
| - | [[Category: Petrini, J H.J]] | + | [[Category: Padjasek M]] |
| - | [[Category: Dna repair]] | + | [[Category: Park YB]] |
| - | [[Category: Hydrolase]] | + | [[Category: Petrini JHJ]] |
| Structural highlights
Disease
RAD50_HUMAN Nijmegen breakage syndrome-like disorder;Hereditary breast and ovarian cancer syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
RAD50_HUMAN Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11A to prevent nucleolytic degradation past a given point (PubMed:11741547, PubMed:9590181, PubMed:9705271, PubMed:9651580). The complex may also be required for DNA damage signaling via activation of the ATM kinase (PubMed:15064416). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
The Rad50 hook interface is crucial for assembly and various functions of the Mre11 complex. Previous analyses suggested that Rad50 molecules interact within (intracomplex) or between (intercomplex) dimeric complexes. In this study, we determined the structure of the human Rad50 hook and coiled-coil domains. The data suggest that the predominant structure is the intracomplex, in which the two parallel coiled coils proximal to the hook form a rod shape, and that a novel interface within the coiled-coil domains of Rad50 stabilizes the interaction of Rad50 protomers in the dimeric assembly. In yeast, removal of the coiled-coil interface compromised Tel1 activation without affecting DNA repair, while simultaneous disruption of that interface and the hook phenocopied a null mutation. The results demonstrate that the hook and coiled-coil interfaces coordinately promote intracomplex assembly and define the intracomplex as the functional form of the Mre11 complex.
Eukaryotic Rad50 functions as a rod-shaped dimer.,Park YB, Hohl M, Padjasek M, Jeong E, Jin KS, Krezel A, Petrini JH, Cho Y Nat Struct Mol Biol. 2017 Mar;24(3):248-257. doi: 10.1038/nsmb.3369. Epub 2017, Jan 30. PMID:28134932[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet. 2000 Jul;25(3):347-52. PMID:10888888 doi:http://dx.doi.org/10.1038/77139
- ↑ de Jager M, van Noort J, van Gent DC, Dekker C, Kanaar R, Wyman C. Human Rad50/Mre11 is a flexible complex that can tether DNA ends. Mol Cell. 2001 Nov;8(5):1129-35. PMID:11741547
- ↑ Lee JH, Paull TT. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science. 2004 Apr 2;304(5667):93-6. PMID:15064416 doi:http://dx.doi.org/10.1126/science.1091496
- ↑ Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR 3rd, Hays L, Morgan WF, Petrini JH. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell. 1998 May 1;93(3):477-86. PMID:9590181
- ↑ Paull TT, Gellert M. The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol Cell. 1998 Jun;1(7):969-79. PMID:9651580
- ↑ Trujillo KM, Yuan SS, Lee EY, Sung P. Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95. J Biol Chem. 1998 Aug 21;273(34):21447-50. PMID:9705271
- ↑ Park YB, Hohl M, Padjasek M, Jeong E, Jin KS, Krezel A, Petrini JH, Cho Y. Eukaryotic Rad50 functions as a rod-shaped dimer. Nat Struct Mol Biol. 2017 Mar;24(3):248-257. doi: 10.1038/nsmb.3369. Epub 2017, Jan 30. PMID:28134932 doi:http://dx.doi.org/10.1038/nsmb.3369
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