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| | ==Crystal structure of the human topoisomerase III alpha-RMI1 complex with bound calcium ion== | | ==Crystal structure of the human topoisomerase III alpha-RMI1 complex with bound calcium ion== |
| - | <StructureSection load='4cht' size='340' side='right' caption='[[4cht]], [[Resolution|resolution]] 3.25Å' scene=''> | + | <StructureSection load='4cht' size='340' side='right'caption='[[4cht]], [[Resolution|resolution]] 3.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4cht]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CHT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CHT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4cht]] 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=4CHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CHT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 3.25Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cgy|4cgy]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase DNA topoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.2 5.99.1.2] </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=4cht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cht OCA], [https://pdbe.org/4cht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cht RCSB], [https://www.ebi.ac.uk/pdbsum/4cht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cht ProSAT]</span></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=4cht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cht OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cht RCSB], [http://www.ebi.ac.uk/pdbsum/4cht PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TOP3A_HUMAN TOP3A_HUMAN]] Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity.<ref>PMID:8622991</ref> <ref>PMID:20445207</ref> [[http://www.uniprot.org/uniprot/RMI1_HUMAN RMI1_HUMAN]] Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability.<ref>PMID:15775963</ref> <ref>PMID:16595695</ref> <ref>PMID:16537486</ref> | + | [https://www.uniprot.org/uniprot/TOP3A_HUMAN TOP3A_HUMAN] Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity.<ref>PMID:8622991</ref> <ref>PMID:20445207</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4cht" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Topoisomerase|Topoisomerase]] | + | *[[Topoisomerase 3D structures|Topoisomerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA topoisomerase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Bocquet, N]] | + | [[Category: Bocquet N]] |
| - | [[Category: Bunker, R D]] | + | [[Category: Bunker RD]] |
| - | [[Category: Thoma, N H]] | + | [[Category: Thoma NH]] |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Decatenation]]
| + | |
| - | [[Category: Double holliday junction dissolution]]
| + | |
| - | [[Category: Minimal dissolvasome]]
| + | |
| Structural highlights
Function
TOP3A_HUMAN Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity.[1] [2]
Publication Abstract from PubMed
Repair of DNA double-strand breaks via homologous recombination can produce double Holliday junctions (dHJs) that require enzymatic separation. Topoisomerase IIIalpha (TopIIIalpha) together with RMI1 disentangles the final hemicatenane intermediate obtained once dHJs have converged. How binding of RMI1 to TopIIIalpha influences it to behave as a hemicatenane dissolvase, rather than as an enzyme that relaxes DNA topology, is unknown. Here, we present the crystal structure of human TopIIIalpha complexed to the first oligonucleotide-binding domain (OB fold) of RMI1. TopIII assumes a toroidal type 1A topoisomerase fold. RMI1 attaches to the edge of the gate in TopIIIalpha through which DNA passes. RMI1 projects a 23-residue loop into the TopIIIalpha gate, thereby influencing the dynamics of its opening and closing. Our results provide a mechanistic rationale for how RMI1 stabilizes TopIIIalpha-gate opening to enable dissolution and illustrate how binding partners modulate topoisomerase function.
Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIalpha and RMI1.,Bocquet N, Bizard AH, Abdulrahman W, Larsen NB, Faty M, Cavadini S, Bunker RD, Kowalczykowski SC, Cejka P, Hickson ID, Thoma NH Nat Struct Mol Biol. 2014 Feb 9. doi: 10.1038/nsmb.2775. PMID:24509834[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hanai R, Caron PR, Wang JC. Human TOP3: a single-copy gene encoding DNA topoisomerase III. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3653-7. PMID:8622991
- ↑ Yang J, Bachrati CZ, Ou J, Hickson ID, Brown GW. Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1. J Biol Chem. 2010 Jul 9;285(28):21426-36. doi: 10.1074/jbc.M110.123216. Epub 2010, May 5. PMID:20445207 doi:http://dx.doi.org/10.1074/jbc.M110.123216
- ↑ Bocquet N, Bizard AH, Abdulrahman W, Larsen NB, Faty M, Cavadini S, Bunker RD, Kowalczykowski SC, Cejka P, Hickson ID, Thoma NH. Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIalpha and RMI1. Nat Struct Mol Biol. 2014 Feb 9. doi: 10.1038/nsmb.2775. PMID:24509834 doi:http://dx.doi.org/10.1038/nsmb.2775
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