MCM8

MCM8
Identifiers
Aliases	MCM8, C20orf154, dJ967N21.5, POF10, minichromosome maintenance 8 homologous recombination repair factor
External IDs	OMIM: 608187 MGI: 1913884 HomoloGene: 12001 GeneCards: MCM8
Gene location (Human)
Chr.	Chromosome 20 (human)[1]
End	5,998,977 bp[1]
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)[2]
End	132,686,117 bp[2]
RNA expression pattern
	Top expressed in
	oocyte; ; secondary oocyte; ; cancellous bone; ; biceps brachii; ; bone marrow cells; ; deltoid muscle; ; gastrocnemius muscle; ; ganglionic eminence; ; stromal cell of endometrium; ; tibialis anterior muscle;
	Top expressed in
	hand; ; secondary oocyte; ; primitive streak; ; abdominal wall; ; maxillary prominence; ; spermatid; ; medial ganglionic eminence; ; morula; ; yolk sac; ; tongue;
	More reference expression data
	n/a
Gene ontology
Molecular function	ATP binding; hydrolase activity; DNA binding; nucleotide binding; helicase activity; protein binding; chromatin binding; enzyme binding; MutLbeta complex binding; MutSalpha complex binding; MutSbeta complex binding; DNA replication origin binding; single-stranded DNA binding;
Cellular component	MCM8-MCM9 complex; nucleus; nucleoplasm; chromosome; MCM complex;
Biological process	female gamete generation; DNA repair; male gamete generation; DNA replication; cell cycle; double-strand break repair via homologous recombination; cellular response to DNA damage stimulus; DNA replication initiation; G1/S transition of mitotic cell cycle; recombinational interstrand cross-link repair; protein stabilization; protein localization to chromatin;
	Sources:Amigo / QuickGO
Orthologs
	84515
	66634
	ENSG00000125885
	ENSMUSG00000027353
	Q9UJA3
	Q9CWV1
	NM_001281520; NM_001281521; NM_001281522; NM_032485; NM_182802
	NM_001291054; NM_025676
	NP_001268449; NP_001268450; NP_001268451; NP_115874; NP_877954
	NP_001277983; NP_079952
	Wikidata
View/Edit Human	View/Edit Mouse

DNA replication licensing factor MCM8 is a protein that in humans is encoded by the MCM8 gene.[5][6]

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein contains the central domain that is conserved among the MCM proteins. This protein has been shown to co-immunoprecipitate with MCM4, 6 and 7, which suggests that it may interact with other MCM proteins and play a role in DNA replication. Alternatively spliced transcript variants encoding distinct isoforms have been described.[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]

A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.

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]

References

GRCh38: Ensembl release 89: ENSG00000125885 - Ensembl, May 2017
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)".
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.
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.
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. Bibcode:2015NatCo...6.7744L. 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.

Volkening M, Hoffmann I (2005). "Involvement of human MCM8 in prereplication complex assembly by recruiting hcdc6 to chromatin". Mol. Cell. Biol. 25 (4): 1560–8. doi:10.1128/MCB.25.4.1560-1568.2005. PMC 548026. PMID 15684404.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Johnson EM, Kinoshita Y, Daniel DC (2003). "A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13". Nucleic Acids Res. 31 (11): 2915–25. doi:10.1093/nar/gkg395. PMC 156728. PMID 12771218.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. Bibcode:2001Natur.414..865D. doi:10.1038/414865a. PMID 11780052.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000125885 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027353 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid12527764-5] 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-6] "Entrez Gene: MCM8 MCM8 minichromosome maintenance deficient 8 (S. cerevisiae)".

[Lutzmann-7] 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.

[Crismani-8] 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.

[Lee-9] 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. Bibcode:2015NatCo...6.7744L. doi:10.1038/ncomms8744. PMC 4525285. PMID 26215093.

[pmid25437880-10] 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.

MCM8

DNA repair

See also

References

Further reading