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| | <StructureSection load='6l0o' size='340' side='right'caption='[[6l0o]], [[Resolution|resolution]] 1.21Å' scene=''> | | <StructureSection load='6l0o' size='340' side='right'caption='[[6l0o]], [[Resolution|resolution]] 1.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6l0o]] is a 1 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=6L0O OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6L0O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6l0o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L0O FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCM8, C20orf154 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCM8, C20orf154 ([https://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/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6l0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l0o OCA], [http://pdbe.org/6l0o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l0o RCSB], [http://www.ebi.ac.uk/pdbsum/6l0o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l0o 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=6l0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l0o OCA], [https://pdbe.org/6l0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l0o RCSB], [https://www.ebi.ac.uk/pdbsum/6l0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l0o ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/MCM8_HUMAN MCM8_HUMAN]] NON RARE IN EUROPE: Primary ovarian failure. The disease is caused by mutations affecting the gene represented in this entry. | + | [[https://www.uniprot.org/uniprot/MCM8_HUMAN MCM8_HUMAN]] NON RARE IN EUROPE: Primary ovarian failure. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MCM8_HUMAN MCM8_HUMAN]] Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR) (PubMed:23401855). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (PubMed:26215093). Probably by regulating the localization of the MNR complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs (PubMed:23401855). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). However, may play a non-essential for DNA replication: may be involved in the activation of the prereplicative complex (pre-RC) during G(1) phase by recruiting CDC6 to the origin recognition complex (ORC) (PubMed:15684404). Probably by regulating HR, plays a key role during gametogenesis (By similarity). Stabilizes MCM9 protein (PubMed:23401855, PubMed:26215093).[UniProtKB:Q9CWV1]<ref>PMID:15684404</ref> <ref>PMID:23401855</ref> <ref>PMID:26215093</ref> | + | [[https://www.uniprot.org/uniprot/MCM8_HUMAN MCM8_HUMAN]] Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR) (PubMed:23401855). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (PubMed:26215093). Probably by regulating the localization of the MNR complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs (PubMed:23401855). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). However, may play a non-essential for DNA replication: may be involved in the activation of the prereplicative complex (pre-RC) during G(1) phase by recruiting CDC6 to the origin recognition complex (ORC) (PubMed:15684404). Probably by regulating HR, plays a key role during gametogenesis (By similarity). Stabilizes MCM9 protein (PubMed:23401855, PubMed:26215093).[UniProtKB:Q9CWV1]<ref>PMID:15684404</ref> <ref>PMID:23401855</ref> <ref>PMID:26215093</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Structural highlights
Disease
[MCM8_HUMAN] NON RARE IN EUROPE: Primary ovarian failure. The disease is caused by mutations affecting the gene represented in this entry.
Function
[MCM8_HUMAN] Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR) (PubMed:23401855). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (PubMed:26215093). Probably by regulating the localization of the MNR complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs (PubMed:23401855). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:23401855). However, may play a non-essential for DNA replication: may be involved in the activation of the prereplicative complex (pre-RC) during G(1) phase by recruiting CDC6 to the origin recognition complex (ORC) (PubMed:15684404). Probably by regulating HR, plays a key role during gametogenesis (By similarity). Stabilizes MCM9 protein (PubMed:23401855, PubMed:26215093).[UniProtKB:Q9CWV1][1] [2] [3]
Publication Abstract from PubMed
Minichromosome maintenance 8 (MCM8) is a recently identified member of the minichromosome maintenance family, which possesses helicase and ATPase activity. It interacts with MCM9 and participates in homologous recombination repair. The structure of MCM8 is unclear now. Here, we report the crystal structure of the winged-helix domain of human MCM8 (MCM8-WHD) at 1.21 A resolution. MCM8-WHD adopts a conserved winged-helix architecture. Structure analysis and biochemical study results showed the DNA binding ability and crucial residues of MCM8-WHD. Our results are helpful to understand the function of MCM8.
Crystal structure of the winged-helix domain of MCM8.,Zeng H, Li J, Xu H, Li H, Liu Y Biochem Biophys Res Commun. 2020 Apr 12. pii: S0006-291X(20)30647-1. doi:, 10.1016/j.bbrc.2020.03.150. PMID:32295713[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Volkening M, Hoffmann I. Involvement of human MCM8 in prereplication complex assembly by recruiting hcdc6 to chromatin. Mol Cell Biol. 2005 Feb;25(4):1560-8. doi: 10.1128/MCB.25.4.1560-1568.2005. PMID:15684404 doi:http://dx.doi.org/10.1128/MCB.25.4.1560-1568.2005
- ↑ Park J, Long DT, Lee KY, Abbas T, Shibata E, Negishi M, Luo Y, Schimenti JC, Gambus A, Walter JC, Dutta A. The MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to facilitate homologous recombination. Mol Cell Biol. 2013 Apr;33(8):1632-44. doi: 10.1128/MCB.01503-12. Epub 2013 Feb, 11. PMID:23401855 doi:http://dx.doi.org/10.1128/MCB.01503-12
- ↑ Lee KY, Im JS, Shibata E, Park J, Handa N, Kowalczykowski SC, Dutta A. MCM8-9 complex promotes resection of double-strand break ends by MRE11-RAD50-NBS1 complex. Nat Commun. 2015 Jul 28;6:7744. doi: 10.1038/ncomms8744. PMID:26215093 doi:http://dx.doi.org/10.1038/ncomms8744
- ↑ Zeng H, Li J, Xu H, Li H, Liu Y. Crystal structure of the winged-helix domain of MCM8. Biochem Biophys Res Commun. 2020 Apr 12. pii: S0006-291X(20)30647-1. doi:, 10.1016/j.bbrc.2020.03.150. PMID:32295713 doi:http://dx.doi.org/10.1016/j.bbrc.2020.03.150
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