MCM10 explained

Protein MCM10 homolog is a protein that in humans is encoded by the MCM10 gene.^{[1] [2] [3]} It is essential for activation of the Cdc45:Mcm2-7:GINS helicase, and thus required for proper DNA replication.^[4]

Function

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The protein complex formed by MCM proteins is a key component of the pre-replication complex (pre-RC) and it may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein can interact with MCM2 and MCM6, as well as with the origin recognition protein ORC2. It is regulated by proteolysis and phosphorylation in a cell cycle-dependent manner. Studies of a similar protein in Xenopus suggest that the chromatin binding of this protein at the onset of DNA replication is after pre-RC assembly and before origin unwinding. Alternatively spliced transcript variants encoding distinct isoforms have been identified.^[3]

Interactions

MCM10 has been shown to interact with ORC2L.

Further reading

• Morimoto S . [Abnormal myocardial contractile regulation mechanism in familial hypertrophic and dilated cardiomyopathies--functional analysis of molecular mutant troponin in in-vitro] . Fukuoka Igaku Zasshi . 93 . 1 . 1–5 . 2002 . 11889827 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Izumi M, Yatagai F, Hanaoka F . Cell cycle-dependent proteolysis and phosphorylation of human Mcm10 . J. Biol. Chem. . 276 . 51 . 48526–31 . 2001 . 11602595 . 10.1074/jbc.M107190200 . free .
• Wohlschlegel JA, Dhar SK, Prokhorova TA, Dutta A, Walter JC . Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45 . Mol. Cell . 9 . 2 . 233–40 . 2002 . 11864598 . 10.1016/S1097-2765(02)00456-2 . free .
• Christensen TW, Tye BK . Drosophila MCM10 interacts with members of the prereplication complex and is required for proper chromosome condensation . Mol. Biol. Cell . 14 . 6 . 2206–15 . 2003 . 12808023 . 194871 . 10.1091/mbc.E02-11-0706 .
• Cook CR, Kung G, Peterson FC, Volkman BF, Lei M . A novel zinc finger is required for Mcm10 homocomplex assembly . J. Biol. Chem. . 278 . 38 . 36051–8 . 2003 . 12844493 . 10.1074/jbc.M306049200 . free .
• Izumi M, Yatagai F, Hanaoka F . Localization of human Mcm10 is spatially and temporally regulated during the S phase . J. Biol. Chem. . 279 . 31 . 32569–77 . 2004 . 15136575 . 10.1074/jbc.M314017200 . free.
• Yoshida K, Inoue I . Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor . Oncogene . 23 . 37 . 6250–60 . 2004 . 15195143 . 10.1038/sj.onc.1207829 . 38885453 .
• Ramachandran N, Hainsworth E, Bhullar B, Eisenstein S, Rosen B, Lau AY, Walter JC, LaBaer J . Self-assembling protein microarrays . Science . 305 . 5680 . 86–90 . 2004 . 15232106 . 10.1126/science.1097639 . 2004Sci...305...86R . 20936301 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Zhu W, Ukomadu C, Jha S, Senga T, Dhar SK, Wohlschlegel JA, Nutt LK, Kornbluth S, Dutta A . Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication . Genes Dev. . 21 . 18 . 2288–99 . 2007 . 17761813 . 1973143 . 10.1101/gad.1585607 .
• Robertson PD, Warren EM, Zhang H, Friedman DB, Lary JW, Cole JL, Tutter AV, Walter JC, Fanning E, Eichman BF . Domain architecture and biochemical characterization of vertebrate Mcm10 . J. Biol. Chem. . 283 . 6 . 3338–48 . 2008 . 18065420 . 2753450 . 10.1074/jbc.M706267200 . free .
• Warren EM, Vaithiyalingam S, Haworth J, Greer B, Bielinsky AK, Chazin WJ, Eichman BF . Structural basis for DNA binding by replication initiator Mcm10 . Structure . 16 . 12 . 1892–901 . 2008 . 19081065 . 2636851 . 10.1016/j.str.2008.10.005 .

Notes and References

1. Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon KY, Hurwitz J, Yatagai F, Hanaoka F . The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase . Nucleic Acids Res. . 28 . 23 . 4769–77 . Dec 2000 . 11095689 . 115166 . 10.1093/nar/28.23.4769 .
2. Chattopadhyay S, Bielinsky AK . Human Mcm10 regulates the catalytic subunit of DNA polymerase-alpha and prevents DNA damage during replication . Mol. Biol. Cell . 18 . 10 . 4085–95 . Sep 2007 . 17699597 . 1995709 . 10.1091/mbc.E06-12-1148 .
3. Web site: Entrez Gene: MCM10 MCM10 minichromosome maintenance deficient 10 (S. cerevisiae).
4. Thu YM, Bielinsky AK . MCM10: one tool for all—Integrity, maintenance and damage control . Seminars in Cell & Developmental Biology . 30 . 121–30 . June 2014 . 24662891 . 10.1016/j.semcdb.2014.03.017 . 4043890 .