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Gene Review

MCM7  -  minichromosome maintenance complex...

Homo sapiens

Synonyms: CDC47, CDC47 homolog, DNA replication licensing factor MCM7, MCM2, P1.1-MCM3, ...
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Disease relevance of MCM7


High impact information on MCM7

  • Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling [6].
  • Such cells show a specific defect in loading of initiator proteins Mcm4, Mcm7, and to a lesser degree, Mcm2 onto chromatin during telophase and early G1 when Mcm2-7 are normally recruited to license origins of replication [7].
  • In HeLa cells, depletion of either hRad17 or hMCM7 with small-interfering RNA suppressed ultraviolet (UV) light- or aphidicolin-induced hChk1 phosphorylation, and abolished UV-induced S-phase checkpoint activation [6].
  • These results demonstrate that hMCM7 plays a direct role in the transmission of DNA damage signals from active replication forks to the S-phase checkpoint machinery in human cells [6].
  • Mcm2, but not RPA, is a component of the mammalian early G1-phase prereplication complex [8].

Chemical compound and disease context of MCM7


Biological context of MCM7


Anatomical context of MCM7


Associations of MCM7 with chemical compounds

  • The p38MAPK inhibitor SB203580, the phosphatidylinositol 3 kinase (PI3-kinase) pathway inhibitor wortmannin, and the protein kinase C pathway (PKC) inhibitor Gö 6976 did not significantly affect mitogen-induced MCM6 and MCM7 expression [11].
  • OBJECTIVE: In an attempt to cast light on the mechanisms governing ATC, we evaluated MCM5 and MCM7 expression in human normal, papillary (PTC), and anaplastic thyroid samples, as well as in primary culture cells and transgenic mouse models [2].
  • CONCLUSIONS: Persistent expression of Mcm2, Mcm5, and Ki-67 proteins in luminal compartments of dysplastic oesophageal squamous epithelium and dysplastic Barrett's mucosa may be diagnostic markers and imply disruption of cell cycle control and differentiation in these dysplastic epithelia [16].
  • Formalin fixed paraffin embedded tissue sections from biopsy series and resections were immunostained using antibodies to Mcm2, Mcm5, and Ki-67 [16].
  • Alanine substitution experiments with Mcm2 peptides showed that the phosphorylation of (5)S and (53)S by Cdc7 required the presence of an acidic amino acid adjacent to a serine residue [17].

Physical interactions of MCM7


Enzymatic interactions of MCM7

  • Mcm7 is ubiquitinated in vivo in both an E6-AP-dependent and -independent manner [21].

Regulatory relationships of MCM7


Other interactions of MCM7

  • MCM6 and MCM7 expression was substantially increased after stimulation with platelet-derived growth factor-BB and insulin [11].
  • MCM7 and its clamp-loading partner Cdc6 are highly specifically colocalized by ChIP and re-ChIP in G(1) and early S on a 198-bp segment located near the center of the initiation zone [10].
  • MCM7 is recruited to multiple sites in chromatin in S and G(2), at which time it is not detected with ORC1 [10].
  • We present our research on the MYCN transcription factor and target gene, MCM7, to show the utility of this approach [23].
  • Interaction of chromatin-associated Plk1 and Mcm7 [18].

Analytical, diagnostic and therapeutic context of MCM7


  1. Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7. Sterner, J.M., Dew-Knight, S., Musahl, C., Kornbluth, S., Horowitz, J.M. Mol. Cell. Biol. (1998) [Pubmed]
  2. Mitogenic effects of the up-regulation of minichromosome maintenance proteins in anaplastic thyroid carcinoma. Guida, T., Salvatore, G., Faviana, P., Giannini, R., Garcia-Rostan, G., Provitera, L., Basolo, F., Fusco, A., Carlomagno, F., Santoro, M. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  3. MCM7 amplification and overexpression are associated with prostate cancer progression. Ren, B., Yu, G., Tseng, G.C., Cieply, K., Gavel, T., Nelson, J., Michalopoulos, G., Yu, Y.P., Luo, J.H. Oncogene (2006) [Pubmed]
  4. Correlation of MYCN amplification with MCM7 protein expression in neuroblastomas: a chromogenic in situ hybridization study in paraffin sections. Tsai, H.Y., Hsi, B.L., Hung, I.J., Yang, C.P., Lin, J.N., Chen, J.C., Tsai, S.F., Huang, S.F. Hum. Pathol. (2004) [Pubmed]
  5. Conditional expression of MCM7 increases tumor growth without altering DNA replication activity. Yoshida, K., Inoue, I. FEBS Lett. (2003) [Pubmed]
  6. Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling. Tsao, C.C., Geisen, C., Abraham, R.T. EMBO J. (2004) [Pubmed]
  7. Deregulation of cyclin E in human cells interferes with prereplication complex assembly. Ekholm-Reed, S., Méndez, J., Tedesco, D., Zetterberg, A., Stillman, B., Reed, S.I. J. Cell Biol. (2004) [Pubmed]
  8. Mcm2, but not RPA, is a component of the mammalian early G1-phase prereplication complex. Dimitrova, D.S., Todorov, I.T., Melendy, T., Gilbert, D.M. J. Cell Biol. (1999) [Pubmed]
  9. DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer. Padmanabhan, V., Callas, P., Philips, G., Trainer, T.D., Beatty, B.G. J. Clin. Pathol. (2004) [Pubmed]
  10. Site-specific loading of an MCM protein complex in a DNA replication initiation zone upstream of the c-MYC gene in the HeLa cell cycle. Kinoshita, Y., Johnson, E.M. J. Biol. Chem. (2004) [Pubmed]
  11. Expression of minichromosome maintenance proteins in vascular smooth muscle cells is ERK/MAPK dependent. Bruemmer, D., Yin, F., Liu, J., Kiyono, T., Fleck, E., Van Herle, A.J., Law, R.E. Exp. Cell Res. (2003) [Pubmed]
  12. Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Cortez, D., Glick, G., Elledge, S.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  13. Comparative analysis of cervical cancer in women and in a human papillomavirus-transgenic mouse model: identification of minichromosome maintenance protein 7 as an informative biomarker for human cervical cancer. Brake, T., Connor, J.P., Petereit, D.G., Lambert, P.F. Cancer Res. (2003) [Pubmed]
  14. Minichromosome maintenance protein 7 expression in gestational trophoblastic disease: correlation with Ki67, PCNA and clinicopathological parameters. Xue, W.C., Khoo, U.S., Ngan, H.Y., Chan, K.Y., Chiu, P.M., Tsao, S.W., Cheung, A.N. Histopathology (2003) [Pubmed]
  15. Identification, molecular cloning, and cellular distribution of the rat homolog of minichromosome maintenance protein 7 (MCM7) in the rat testis. Com, E., Rolland, A.D., Guerrois, M., Aubry, F., Jégou, B., Vallet-Erdtmann, V., Pineau, C. Mol. Reprod. Dev. (2006) [Pubmed]
  16. Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in dysplastic squamous oesophageal epithelium and Barrett's mucosa. Going, J.J., Keith, W.N., Neilson, L., Stoeber, K., Stuart, R.C., Williams, G.H. Gut (2002) [Pubmed]
  17. CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein. Cho, W.H., Lee, Y.J., Kong, S.I., Hurwitz, J., Lee, J.K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  18. Interaction of chromatin-associated Plk1 and Mcm7. Tsvetkov, L., Stern, D.F. J. Biol. Chem. (2005) [Pubmed]
  19. The cell cycle regulator p27Kip1 interacts with MCM7, a DNA replication licensing factor, to inhibit initiation of DNA replication. Nallamshetty, S., Crook, M., Boehm, M., Yoshimoto, T., Olive, M., Nabel, E.G. FEBS Lett. (2005) [Pubmed]
  20. Protein-protein interaction of FHL2, a LIM domain protein preferentially expressed in human heart, with hCDC47. Chan, K.K., Tsui, S.K., Ngai, S.M., Lee, S.M., Kotaka, M., Waye, M.M., Lee, C.Y., Fung, K.P. J. Cell. Biochem. (2000) [Pubmed]
  21. E3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box. Kühne, C., Banks, L. J. Biol. Chem. (1998) [Pubmed]
  22. hCDC47, a human member of the MCM family. Dissociation of the nucleus-bound form during S phase. Fujita, M., Kiyono, T., Hayashi, Y., Ishibashi, M. J. Biol. Chem. (1996) [Pubmed]
  23. Gene profiling of high risk neuroblastoma. Vasudevan, S.A., Nuchtern, J.G., Shohet, J.M. World journal of surgery. (2005) [Pubmed]
  24. Mammalian Mcm2/4/6/7 complex forms a toroidal structure. Yabuta, N., Kajimura, N., Mayanagi, K., Sato, M., Gotow, T., Uchiyama, Y., Ishimi, Y., Nojima, H. Genes Cells (2003) [Pubmed]
  25. Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication. Jiang, W., McDonald, D., Hope, T.J., Hunter, T. EMBO J. (1999) [Pubmed]
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