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Gene Review

MCM6  -  minichromosome maintenance complex...

Homo sapiens

Synonyms: DNA replication licensing factor MCM6, MCG40308, Mis5, P105MCM, p105MCM
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Disease relevance of MCM6

  • Since the level of cell proliferation is the most valuable predictor of survival in mantle cell lymphoma (MCL), we investigated lymph node biopsy specimens from 70 patients immunohistochemically with a monoclonal antibody against MCM6 [1].
  • The percentage of MCM6 expressing lymphoma cells ranged from 12.0 to 95.6%, with a mean of 61.0%, and was significantly higher than the percentage of Ki-67-positive cells (P<0.0001) [1].

High impact information on MCM6

  • This single nucleotide polymorphism is located 14 kb upstream from the start of transcription of lactase in an intron of the adjacent gene MCM6 [2].
  • These results are consistent with the notion that the N-terminal phosphorylation of MCM2, MCM4, and MCM6 may play functionally redundant but essential roles in initiation of DNA replication [3].
  • MCM4 and MCM6 are also phosphorylated by huCdc7 albeit to less extent [4].
  • Inhibition of licensing with 6-dimethylaminopurine results in chromatin containing specifically bound MCM4 and MCM6 [5].
  • MCM6 and MCM7 expression was substantially increased after stimulation with platelet-derived growth factor-BB and insulin [6].

Biological context of MCM6

  • The present studies were designed to investigate the signal transduction pathways controlling the expression of MCM6 and MCM7 in VSMC in response to mitogenic stimuli [6].
  • Transient transfection experiments revealed that PD98059 inhibited mitogen-induced MCM6 and MCM7 transcriptional activation [6].
  • Minichromosome maintenance protein 6 (MCM6) is one of six proteins of the MCM family which are involved in the initiation of DNA replication and thus represent a marker of proliferating cells [1].
  • Therefore, aside from gene expression profiling, immunohistochemical detection of MCM6 seems to be the most promising marker for predicting the outcome in MCL [1].
  • Surprisingly, the ratio of MCM6-positive cells to Ki-67-positive cells was higher than in normal stimulated peripheral blood mononuclear cells, indicating a cell early G1-phase arrest in MCL [1].

Anatomical context of MCM6


  1. Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma. Schrader, C., Janssen, D., Klapper, W., Siebmann, J.U., Meusers, P., Brittinger, G., Kneba, M., Tiemann, M., Parwaresch, R. Br. J. Cancer (2005) [Pubmed]
  2. Genetics of lactase persistence and lactose intolerance. Swallow, D.M. Annu. Rev. Genet. (2003) [Pubmed]
  3. Phosphorylation of MCM4 by Cdc7 Kinase Facilitates Its Interaction with Cdc45 on the Chromatin. Masai, H., Taniyama, C., Ogino, K., Matsui, E., Kakusho, N., Matsumoto, S., Kim, J.M., Ishii, A., Tanaka, T., Kobayashi, T., Tamai, K., Ohtani, K., Arai, K. J. Biol. Chem. (2006) [Pubmed]
  4. Human Cdc7-related kinase complex. In vitro phosphorylation of MCM by concerted actions of Cdks and Cdc7 and that of a criticial threonine residue of Cdc7 bY Cdks. Masai, H., Matsui, E., You, Z., Ishimi, Y., Tamai, K., Arai, K. J. Biol. Chem. (2000) [Pubmed]
  5. Stepwise regulated chromatin assembly of MCM2-7 proteins. Maiorano, D., Lemaître, J.M., Méchali, M. J. Biol. Chem. (2000) [Pubmed]
  6. 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]
  7. Notch-dependent cell cycle arrest is associated with downregulation of minichromosome maintenance proteins. Noseda, M., Niessen, K., McLean, G., Chang, L., Karsan, A. Circ. Res. (2005) [Pubmed]
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