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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]}

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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