MCM2 explained

DNA replication licensing factor MCM2 is a protein that in humans is encoded by the MCM2 gene.^{[1] [2]}

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 hexameric protein complex formed by 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 forms a complex with MCM4, 6, and 7, and has been shown to regulate the helicase activity of the complex. This protein is phosphorylated, and thus regulated by, protein kinases CDC2 and CDC7.^[3]

Interactions

MCM2 has been shown to interact with:

• AKAP8,^[4]
• Cell division cycle 7-related protein kinase,
• MCM3,
• MCM4,^[5]
• MCM5,^[6]
• MCM6,^{[7] [8] [9] [10]}
• MCM7,^{[7] [8] [10] [11]}
• ORC1L,
• ORC2L,
• ORC4L,
• ORC5L, and
• Replication protein A1.^[12]

See also

• Mini Chromosome Maintenance

Further reading

• Nomura N, Miyajima N, Sazuka T, Tanaka A, Kawarabayasi Y, Sato S, Nagase T, Seki N, Ishikawa K, Tabata S . Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1. . DNA Res. . 1 . 1 . 27–35 . 1995 . 7584026 . 10.1093/dnares/1.1.27 . free .
• Nomura N, Miyajima N, Sazuka T, Tanaka A, Kawarabayasi Y, Sato S, Nagase T, Seki N, Ishikawa K, Tabata S . Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 (supplement). . DNA Res. . 1 . 1 . 47–56 . 1995 . 7584028 . 10.1093/dnares/1.1.47 . free .
• Nakatsuru S, Sudo K, Nakamura Y . Isolation and mapping of a human gene (MCM2) encoding a product homologous to yeast proteins involved in DNA replication. . Cytogenet. Cell Genet. . 68 . 3–4 . 226–30 . 1995 . 7842741 . 10.1159/000133918 .
• Todorov IT, Pepperkok R, Philipova RN, Kearsey SE, Ansorge W, Werner D . A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division . J. Cell Sci. . 107 . 1 . 253–65 . 1994 . 10.1242/jcs.107.1.253 . 8175912 .
• Ishimi Y, Ichinose S, Omori A, Sato K, Kimura H . Binding of human minichromosome maintenance proteins with histone H3 . J. Biol. Chem. . 271 . 39 . 24115–22 . 1996 . 8798650 . 10.1074/jbc.271.39.24115 . free .
• Fujita M, Yamada C, Tsurumi T, Hanaoka F, Matsuzawa K, Inagaki M . Cell cycle- and chromatin binding state-dependent phosphorylation of human MCM heterohexameric complexes. A role for cdc2 kinase . J. Biol. Chem. . 273 . 27 . 17095–101 . 1998 . 9642275 . 10.1074/jbc.273.27.17095 . free .
• Jiang W, McDonald D, Hope TJ, Hunter T . Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication . EMBO J. . 18 . 20 . 5703–13 . 1999 . 10523313 . 1171637 . 10.1093/emboj/18.20.5703 .
• You Z, Komamura Y, Ishimi Y . Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity . Mol. Cell. Biol. . 19 . 12 . 8003–15 . 2000 . 10567526 . 84885 . 10.1128/MCB.19.12.8003.
• Ishimi Y, Komamura-Kohno Y, You Z, Omori A, Kitagawa M . Inhibition of Mcm4,6,7 helicase activity by phosphorylation with cyclin A/Cdk2 . J. Biol. Chem. . 275 . 21 . 16235–41 . 2000 . 10748114 . 10.1074/jbc.M909040199 . free .
• Masai H, Matsui E, You Z, Ishimi Y, Tamai K, Arai K . Human Cdc7-related kinase complex. In vitro phosphorylation of MCM by concerted actions of Cdks and Cdc7 and that of a critical threonine residue of Cdc7 bY Cdks . J. Biol. Chem. . 275 . 37 . 29042–52 . 2000 . 10846177 . 10.1074/jbc.M002713200 . free .
• 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 . 2001 . 11095689 . 115166 . 10.1093/nar/28.23.4769 .
• Burke TW, Cook JG, Asano M, Nevins JR . Replication factors MCM2 and ORC1 interact with the histone acetyltransferase HBO1 . J. Biol. Chem. . 276 . 18 . 15397–408 . 2001 . 11278932 . 10.1074/jbc.M011556200 . free .
• Tan DF, Huberman JA, Hyland A, Loewen GM, Brooks JS, Beck AF, Todorov IT, Bepler G . MCM2--a promising marker for premalignant lesions of the lung: a cohort study . BMC Cancer . 1 . 6 . 2002 . 11472637 . 35283 . 10.1186/1471-2407-1-6 . free .
• Ishimi Y, Komamura-Kohno Y, Arai K, Masai H . Biochemical activities associated with mouse Mcm2 protein . J. Biol. Chem. . 276 . 46 . 42744–52 . 2001 . 11568184 . 10.1074/jbc.M106861200 . 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 .
• Kodani I, Shomori K, Osaki M, Kuratate I, Ryoke K, Ito H . Expression of minichromosome maintenance 2 (MCM2), Ki-67, and cell-cycle-related molecules, and apoptosis in the normal-dysplasia-carcinoma sequence of the oral mucosa . Pathobiology . 69 . 3 . 150–8 . 2002 . 11872961 . 10.1159/000048770 . 11047685 .
• Edwards MC, Tutter AV, Cvetic C, Gilbert CH, Prokhorova TA, Walter JC . MCM2-7 complexes bind chromatin in a distributed pattern surrounding the origin recognition complex in Xenopus egg extracts . J. Biol. Chem. . 277 . 36 . 33049–57 . 2002 . 12087101 . 10.1074/jbc.M204438200 . free .
• Osaki M, Osaki M, Yamashita H, Shomori K, Yoshida H, Ito H . Expression of minichromosome maintenance-2 in human malignant fibrous histiocytomas: Correlations with Ki-67 and P53 expression, and apoptosis . Int. J. Mol. Med. . 10 . 2 . 161–8 . 2003 . 12119552 . 10.3892/ijmm.10.2.161 .

Notes and References

1. Todorov IT, Lavigne J, Sakr F, Kaneva R, Foisy S, Bibor-Hardy V . Nuclear matrix protein mitotin messenger RNA is expressed at constant levels during the cell cycle . Biochem Biophys Res Commun . 177 . 1 . 395–400 . Jul 1991 . 1710453 . 10.1016/0006-291X(91)91996-P .
2. Mincheva A, Todorov I, Werner D, Fink TM, Lichter P . The human gene for nuclear protein BM28 (CDCL1), a new member of the early S-phase family of proteins, maps to chromosome band 3q21 . Cytogenet Cell Genet . 65 . 4 . 276–7 . Jan 1994 . 8258304 . 10.1159/000133647 .
3. Web site: Entrez Gene: MCM2 MCM2 minichromosome maintenance deficient 2, mitotin (S. cerevisiae).
4. Eide T, Taskén KA, Carlson C, Williams G, Jahnsen T, Taskén K, Collas P . Protein kinase A-anchoring protein AKAP95 interacts with MCM2, a regulator of DNA replication . J. Biol. Chem. . 278 . 29 . 26750–6 . Jul 2003 . 12740381 . 10.1074/jbc.M300765200 . free .
5. Ishimi Y, Ichinose S, Omori A, Sato K, Kimura H . Binding of human minichromosome maintenance proteins with histone H3 . J. Biol. Chem. . 271 . 39 . 24115–22 . Sep 1996 . 8798650 . 10.1074/jbc.271.39.24115. free .
6. DaFonseca CJ, Shu F, Zhang JJ . Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-gamma . Proc. Natl. Acad. Sci. U.S.A. . 98 . 6 . 3034–9 . Mar 2001 . 11248027 . 30602 . 10.1073/pnas.061487598 . 2001PNAS...98.3034D . free .
7. Yabuta N, Kajimura N, Mayanagi K, Sato M, Gotow T, Uchiyama Y, Ishimi Y, Nojima H . Mammalian Mcm2/4/6/7 complex forms a toroidal structure . Genes Cells . 8 . 5 . 413–21 . May 2003 . 12694531 . 10.1046/j.1365-2443.2003.00645.x. 27707848 . free .
8. You Z, Komamura Y, Ishimi Y . Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity . Mol. Cell. Biol. . 19 . 12 . 8003–15 . Dec 1999 . 10567526 . 84885 . 10.1128/MCB.19.12.8003.
9. 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 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
10. You Z, Ishimi Y, Masai H, Hanaoka F . Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex . J. Biol. Chem. . 277 . 45 . 42471–9 . Nov 2002 . 12207017 . 10.1074/jbc.M205769200 . free .
11. Fujita M, Kiyono T, Hayashi Y, Ishibashi M . In vivo interaction of human MCM heterohexameric complexes with chromatin. Possible involvement of ATP . J. Biol. Chem. . 272 . 16 . 10928–35 . Apr 1997 . 9099751 . 10.1074/jbc.272.16.10928. free .
12. Kneissl M, Pütter V, Szalay AA, Grummt F . Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells . J. Mol. Biol. . 327 . 1 . 111–28 . Mar 2003 . 12614612 . 10.1016/s0022-2836(03)00079-2.