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| | ==Structure of the S. pombe Nbs1-Ctp1 complex== | | ==Structure of the S. pombe Nbs1-Ctp1 complex== |
| - | <StructureSection load='3huf' size='340' side='right' caption='[[3huf]], [[Resolution|resolution]] 2.15Å' scene=''> | + | <StructureSection load='3huf' size='340' side='right'caption='[[3huf]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3huf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Cbs_356 Cbs 356]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HUF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HUF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3huf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe Schizosaccharomyces pombe]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HUF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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]] 2.15Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hue|3hue]]</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=3huf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3huf OCA], [https://pdbe.org/3huf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3huf RCSB], [https://www.ebi.ac.uk/pdbsum/3huf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3huf ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nbs1, SPBC6B1.09c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4896 CBS 356])</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=3huf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3huf OCA], [http://pdbe.org/3huf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3huf RCSB], [http://www.ebi.ac.uk/pdbsum/3huf PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NBS1_SCHPO NBS1_SCHPO]] Required for DNA damage repair and S-phase DNA damage checkpoint. Involved in telomere length maintenance and maintenance of chromatin structure.<ref>PMID:12944481</ref> <ref>PMID:12944482</ref> [[http://www.uniprot.org/uniprot/COM1_SCHPO COM1_SCHPO]] Endonuclease that cooperates with the MRN complex in processing meiotic and mitotic double-strand breaks by allowing the endonucleolytic removal of rec12 from the break sites and ensuring both resection and intrachromosomal association of the broken ends. Required for the formation of RPA-coated single strand DNA adjacent to the DSBs where it functions together with the MRN complex in 5'- 3' resection. Required for the repair of programmed meiotic DSBs. Involved also in an rhp51 recombinase-dependent recombinational repair pathway.<ref>PMID:16303567</ref> <ref>PMID:17936710</ref> <ref>PMID:18378696</ref> <ref>PMID:19139281</ref> | + | [https://www.uniprot.org/uniprot/NBS1_SCHPO NBS1_SCHPO] Required for DNA damage repair and S-phase DNA damage checkpoint. Involved in telomere length maintenance and maintenance of chromatin structure.<ref>PMID:12944481</ref> <ref>PMID:12944482</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hu/3huf_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hu/3huf_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cbs 356]] | + | [[Category: Large Structures]] |
| - | [[Category: Guenther, G]] | + | [[Category: Schizosaccharomyces pombe]] |
| - | [[Category: Tainer, J A]] | + | [[Category: Guenther G]] |
| - | [[Category: Williams, R S]] | + | [[Category: Tainer JA]] |
| - | [[Category: Brct domain]] | + | [[Category: Williams RS]] |
| - | [[Category: Cell cycle]]
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| - | [[Category: Chromosomal protein]]
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| - | [[Category: Ctp1]]
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| - | [[Category: Dna damage]]
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| - | [[Category: Dna repair]]
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| - | [[Category: Fha domain]]
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| - | [[Category: Meiosis]]
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| - | [[Category: Nbs1]]
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| - | [[Category: Nucleus]]
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| - | [[Category: Phosphoprotein]]
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| - | [[Category: Phosphoprotein binding]]
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| - | [[Category: Phosphoserine binding]]
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| - | [[Category: Telomere]]
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| Structural highlights
Function
NBS1_SCHPO Required for DNA damage repair and S-phase DNA damage checkpoint. Involved in telomere length maintenance and maintenance of chromatin structure.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Nijmegen breakage syndrome 1 (Nbs1) subunit of the Mre11-Rad50-Nbs1 (MRN) complex protects genome integrity by coordinating double-strand break (DSB) repair and checkpoint signaling through undefined interactions with ATM, MDC1, and Sae2/Ctp1/CtIP. Here, fission yeast and human Nbs1 structures defined by X-ray crystallography and small angle X-ray scattering (SAXS) reveal Nbs1 cardinal features: fused, extended, FHA-BRCT(1)-BRCT(2) domains flexibly linked to C-terminal Mre11- and ATM-binding motifs. Genetic, biochemical, and structural analyses of an Nbs1-Ctp1 complex show Nbs1 recruits phosphorylated Ctp1 to DSBs via binding of the Nbs1 FHA domain to a Ctp1 pThr-Asp motif. Nbs1 structures further identify an extensive FHA-BRCT interface, a bipartite MDC1-binding scaffold, an extended conformational switch, and the molecular consequences associated with cancer predisposing Nijmegen breakage syndrome mutations. Tethering of Ctp1 to a flexible Nbs1 arm suggests a mechanism for restricting DNA end processing and homologous recombination activities of Sae2/Ctp1/CtIP to the immediate vicinity of DSBs.
Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair.,Williams RS, Dodson GE, Limbo O, Yamada Y, Williams JS, Guenther G, Classen S, Glover JN, Iwasaki H, Russell P, Tainer JA Cell. 2009 Oct 2;139(1):87-99. PMID:19804755[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ueno M, Nakazaki T, Akamatsu Y, Watanabe K, Tomita K, Lindsay HD, Shinagawa H, Iwasaki H. Molecular characterization of the Schizosaccharomyces pombe nbs1+ gene involved in DNA repair and telomere maintenance. Mol Cell Biol. 2003 Sep;23(18):6553-63. PMID:12944481
- ↑ Chahwan C, Nakamura TM, Sivakumar S, Russell P, Rhind N. The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint. Mol Cell Biol. 2003 Sep;23(18):6564-73. PMID:12944482
- ↑ Williams RS, Dodson GE, Limbo O, Yamada Y, Williams JS, Guenther G, Classen S, Glover JN, Iwasaki H, Russell P, Tainer JA. Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair. Cell. 2009 Oct 2;139(1):87-99. PMID:19804755 doi:10.1016/j.cell.2009.07.033
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