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| | ==Crystal structure of the RMI core complex with MM2 peptide from FANCM== | | ==Crystal structure of the RMI core complex with MM2 peptide from FANCM== |
| - | <StructureSection load='4day' size='340' side='right' caption='[[4day]], [[Resolution|resolution]] 3.30Å' scene=''> | + | <StructureSection load='4day' size='340' side='right'caption='[[4day]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4day]] is a 3 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=4DAY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DAY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4day]] is a 3 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=4DAY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DAY FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mxn|3mxn]], [[3nbh|3nbh]]</td></tr> | + | </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=4day FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4day OCA], [https://pdbe.org/4day PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4day RCSB], [https://www.ebi.ac.uk/pdbsum/4day PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4day ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RMI1, C9orf76 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RMI2, C16orf75 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FANCM, KIAA1596 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </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=4day FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4day OCA], [http://pdbe.org/4day PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4day RCSB], [http://www.ebi.ac.uk/pdbsum/4day PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4day ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN]] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[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> [[http://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN]] ATPase required for FANCD2 ubiquitination, a key reaction in DNA repair. Binds to ssDNA but not to dsDNA. Recruited to forks stalled by DNA interstrand cross-links, and required for cellular resistance to such lesions.<ref>PMID:16116422</ref> <ref>PMID:16116434</ref> [REFERENCE:7][REFERENCE:8] [[http://www.uniprot.org/uniprot/RMI2_HUMAN RMI2_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. The complex is therefore essential for the stability, localization, and function of complexes containing BLM. In the RMI complex, it is required to target BLM to chromatin and stress-induced nuclear foci and mitotic phosphorylation of BLM.<ref>PMID:18923082</ref> <ref>PMID:18923083</ref> | + | [[https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: RNA helicase]] | + | [[Category: Large Structures]] |
| - | [[Category: Hoadley, K A]] | + | [[Category: Hoadley KA]] |
| - | [[Category: Keck, J L]] | + | [[Category: Keck JL]] |
| - | [[Category: Ob fold]]
| + | |
| - | [[Category: Protein binding-hydrolase complex]]
| + | |
| Structural highlights
Function
[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.[1] [2] [3]
Publication Abstract from PubMed
The RMI subcomplex (RMI1/RMI2) functions with the BLM helicase and topoisomerase IIIalpha in a complex called the "dissolvasome," which separates double-Holliday junction DNA structures that can arise during DNA repair. This activity suppresses potentially harmful sister chromatid exchange (SCE) events in wild-type cells but not in cells derived from Bloom syndrome patients with inactivating BLM mutations. The RMI subcomplex also associates with FANCM, a component of the Fanconi anemia (FA) core complex that is important for repair of stalled DNA replication forks. The RMI/FANCM interface appears to help coordinate dissolvasome and FA core complex activities, but its precise role remains poorly understood. Here, we define the structure of the RMI/FANCM interface and investigate its roles in coordinating cellular DNA-repair activities. The X-ray crystal structure of the RMI core complex bound to a well-conserved peptide from FANCM shows that FANCM binds to both RMI proteins through a hydrophobic "knobs-into-holes" packing arrangement. The RMI/FANCM interface is shown to be critical for interaction between the components of the dissolvasome and the FA core complex. FANCM variants that substitute alanine for key interface residues strongly destabilize the complex in solution and lead to increased SCE levels in cells that are similar to those observed in blm- or fancm-deficient cells. This study provides a molecular view of the RMI/FANCM complex and highlights a key interface utilized in coordinating the activities of two critical eukaryotic DNA-damage repair machines.
Defining the molecular interface that connects the Fanconi anemia protein FANCM to the Bloom syndrome dissolvasome.,Hoadley KA, Xue Y, Ling C, Takata M, Wang W, Keck JL Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4437-42. Epub 2012 Mar 5. PMID:22392978[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yin J, Sobeck A, Xu C, Meetei AR, Hoatlin M, Li L, Wang W. BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. EMBO J. 2005 Apr 6;24(7):1465-76. Epub 2005 Mar 17. PMID:15775963 doi:http://dx.doi.org/7600622
- ↑ Raynard S, Bussen W, Sung P. A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75. J Biol Chem. 2006 May 19;281(20):13861-4. Epub 2006 Apr 4. PMID:16595695 doi:http://dx.doi.org/C600051200
- ↑ Wu L, Bachrati CZ, Ou J, Xu C, Yin J, Chang M, Wang W, Li L, Brown GW, Hickson ID. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4068-73. Epub 2006 Mar 6. PMID:16537486 doi:http://dx.doi.org/10.1073/pnas.0508295103
- ↑ Hoadley KA, Xue Y, Ling C, Takata M, Wang W, Keck JL. Defining the molecular interface that connects the Fanconi anemia protein FANCM to the Bloom syndrome dissolvasome. Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4437-42. Epub 2012 Mar 5. PMID:22392978 doi:10.1073/pnas.1117279109
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