MCM8
MCM8 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | MCM8, C20orf154, dJ967N21.5, POF10, minichromosome maintenance 8 homologous recombination repair factor | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 608187; MGI: 1913884; HomoloGene: 12001; GeneCards: MCM8; OMA:MCM8 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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DNA replication licensing factor MCM8 is a protein that in humans is encoded by the MCM8 gene.[5][6]
DNA repair
MCM8-deficient mice are defective in gametogenesis and display genome instability due to impaired homologous recombination.[7] Male MCM8 (-/-) mice are sterile because spermatocytes are blocked in meiotic prophase I. Female MCM8(-/-) mice have arrested primary follicles and frequently develop ovarian tumors.[7] MCM8 protein forms a complex with MCM9.
In the plant Arabidopsis thaliana, MCM8 is required for a pathway of meiotic DNA double-strand break repair.[8] It was proposed that MCM8 is involved with RAD51 in a backup pathway that repairs meiotic double-strand breaks without yielding crossovers when the major recombination pathway, which relies on DMC1, fails.[8]
MCM8 forms a complex with MCM9 that is required for DNA resection by the MRN complex (MRE11-RAD50-NBS1) at double strand breaks to generate single-stranded DNA ends.[9] The formation of single-strand ends is an early step in homologous recombination (see Figure). MCM8/MCM9 interacts with MRN and is required for the nuclease action and stable association of MRN with double-strand breaks.[9]
In humans, an MCM8 mutation can give rise to premature ovarian failure, as well as chromosomal instability.[10]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000125885 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027353 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Gozuacik D, Chami M, Lagorce D, Faivre J, Murakami Y, Poch O, Biermann E, Knippers R, Brechot C, Paterlini-Brechot P (Jan 2003). "Identification and functional characterization of a new member of the human Mcm protein family: hMcm8". Nucleic Acids Res. 31 (2): 570–9. doi:10.1093/nar/gkg136. PMC 140502. PMID 12527764.
- ^ "Entrez Gene: MCM8 MCM8 minichromosome maintenance deficient 8 (S. cerevisiae)".
- ^ a b Lutzmann M, Grey C, Traver S, Ganier O, Maya-Mendoza A, Ranisavljevic N, Bernex F, Nishiyama A, Montel N, Gavois E, Forichon L, de Massy B, Méchali M (2012). "MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination". Mol. Cell. 47 (4): 523–34. doi:10.1016/j.molcel.2012.05.048. PMID 22771120.
- ^ a b Crismani W, Portemer V, Froger N, Chelysheva L, Horlow C, Vrielynck N, Mercier R (2013). "MCM8 is required for a pathway of meiotic double-strand break repair independent of DMC1 in Arabidopsis thaliana". PLoS Genet. 9 (1): e1003165. doi:10.1371/journal.pgen.1003165. PMC 3536722. PMID 23300481.
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: CS1 maint: unflagged free DOI (link) - ^ a b Lee KY, Im JS, Shibata E, Park J, Handa N, Kowalczykowski SC, Dutta A (2015). "MCM8-9 complex promotes resection of double-strand break ends by MRE11-RAD50-NBS1 complex". Nat Commun. 6: 7744. doi:10.1038/ncomms8744. PMC 4525285. PMID 26215093.
- ^ AlAsiri S, Basit S, Wood-Trageser MA, Yatsenko SA, Jeffries EP, Surti U, Ketterer DM, Afzal S, Ramzan K, Faiyaz-Ul Haque M, Jiang H, Trakselis MA, Rajkovic A (2015). "Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability". J. Clin. Invest. 125 (1): 258–62. doi:10.1172/JCI78473. PMC 4382257. PMID 25437880.
Further reading