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Gene Review

Mcm3  -  minichromosome maintenance deficient 3 (S....

Mus musculus

Synonyms: AL033361, C80350, DNA polymerase alpha holoenzyme-associated protein P1, DNA replication licensing factor MCM3, Mcmd, ...
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Disease relevance of Mcm3

  • To generate mosaic animals, we used the bacteriophage P1-derived Cre-loxP recombination system, which allows gene alteration by Cre-mediated deletion of loxP-flanked gene segments [1].
  • Monoclonal antibodies to the class 1 outer membrane protein P1 of Neisseria meningitidis B:15:P1.7,16 have been shown to be bactericidal and protective in an infant rat meningitis model [2].
  • We have produced the P1 protein in Bacillus subtilis as inclusion bodies [2].
  • The first DNA vaccine, pP12X3C, encodes the viral capsid gene (P1) and the processing proteinase (3C) [3].
  • The brain samples were retested for rabies by means of the reverse transcription and polymerase chain reaction (RT-PCR) with 2 primer sets (P1/P2 and RHNI/RHNS3), which amplified full or partial regions on the nucleoprotein (N) gene of the rabies virus, respectively [4].

High impact information on Mcm3

  • Thus, it is likely that the underphosphorylated P1 is dissociated from the nuclear structure after DNA replication by cell cycle-dependent phosphorylation [5].
  • Using a polyclonal anti-P1 antibody raised against a beta-galactosidase-P1 fusion protein, we identified at least two forms of P1 protein in the nucleus of a mouse cell line, an underphosphorylated form that was associated with a particular nuclear structure and a hyperphosphorylated form loosely bound to the nucleus [5].
  • During progression through S phase, P1 disappeared, first from the euchromatic region, then from the heterochromatic region, apparently in parallel with temporally ordered DNA replication [5].
  • Low stringency screening of a human P1 artificial chromosome library using a human hair keratin-associated protein (hKAP1.1A) gene probe resulted in the isolation of six P1 artificial chromosome clones [6].
  • Analysis by reverse transcription-polymerase chain reaction shows that promoters P1 and P2 are utilized in osteoclasts, brain, and kidney, whereas promoter P3 appears to be osteoclast-specific [7].

Chemical compound and disease context of Mcm3


Biological context of Mcm3

  • Throughout its length, the primary structure of mammalian P1 displayed strong homology with that of Mcm3, a 125 kDa yeast protein thought to be involved in the initiation of DNA replication (Gibson et al. 1990. Mol. Cell. Biol. 10: 5707-5720) [8].
  • Depletion of Orc2 and Mcm3 by siRNA leads to an inhibition of cell proliferation, an altered cell cycle distribution as well as to multinucleated cells with insufficiently organised microtubules [9].
  • Detailed analysis of the intranuclear localization of the P1 protein during the cell cycle revealed that it accumulates transiently in the heterochromatic regions towards the end of G1 [10].
  • We found that the murine P1 protein was present in the nuclei of mammalian cells throughout interphase of the cell cycle [10].
  • The chromosomal localization of the P1 gene was determined by fluorescence in situ hybridization to region 6p12 in human metaphase chromosomes [10].

Anatomical context of Mcm3


Associations of Mcm3 with chemical compounds

  • These results demonstrate that AMP phosphohydrolase activity in NG108-15 cells is due to ecto-ALP, and suggest that this enzyme plays an essential role for the P1 antagonist-sensitive ATP-induced cyclic AMP accumulation in NG108-15 cells [15].
  • Further variants comprising DDDDK(156)SS, DDDDK(156)SD and DDDDK(156)RR showed that the minimal critical determinants for enhanced enterokinase cleavage are serine in the P1' position followed by a serine or a basic residue, lysine or arginine, in the P2' position [16].

Physical interactions of Mcm3

  • Ciz1-depleted cells accumulate with chromatin bound Mcm3 and PCNA but fail to synthesize DNA efficiently [17].

Analytical, diagnostic and therapeutic context of Mcm3

  • METHODS AND RESULTS: Using polymerase chain reaction (PCR) and direct automated sequencing, a biallelic (A/C) polymorphism was detected at position -55 in a conserved promoter element named P1 [18].
  • Furthermore, a minor start site was localized 179 bp upstream of the major site using reverse transcriptase-polymerase chain reaction with various P1 primers (primer walking), primer extension, and cDNA cloning [19].
  • The resulting antisera contained high titers (enzyme immunoassay) of antibodies directed to native P1 epitopes exposed on the surface of meningococcal cells [2].


  1. Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination. Betz, U.A., Vosshenrich, C.A., Rajewsky, K., Müller, W. Curr. Biol. (1996) [Pubmed]
  2. The antibody response to a prototype liposome vaccine containing Neisseria meningitidis outer membrane protein P1 produced in Bacillus subtilis. Idänpään-Heikkilä, I., Muttilainen, S., Wahlström, E., Saarinen, L., Leinonen, M., Sarvas, M., Mäkelä, P.H. Vaccine (1995) [Pubmed]
  3. Development of DNA vaccines for foot-and-mouth disease, evaluation of vaccines encoding replicating and non-replicating nucleic acids in swine. Beard, C., Ward, G., Rieder, E., Chinsangaram, J., Grubman, M.J., Mason, P.W. J. Biotechnol. (1999) [Pubmed]
  4. Detection of rabies virus RNA isolated from several species of animals in Brazil by RT-PCR. Ito, M., Itou, T., Sakai, T., Santos, M.F., Arai, Y.T., Takasaki, T., Kurane, I., Ito, F.H. J. Vet. Med. Sci. (2001) [Pubmed]
  5. DNA polymerase alpha associated protein P1, a murine homolog of yeast MCM3, changes its intranuclear distribution during the DNA synthetic period. Kimura, H., Nozaki, N., Sugimoto, K. EMBO J. (1994) [Pubmed]
  6. Characterization of a cluster of human high/ultrahigh sulfur keratin-associated protein genes embedded in the type I keratin gene domain on chromosome 17q12-21. Rogers, M.A., Langbein, L., Winter, H., Ehmann, C., Praetzel, S., Korn, B., Schweizer, J. J. Biol. Chem. (2001) [Pubmed]
  7. Tissue-specific and ubiquitous promoters direct the expression of alternatively spliced transcripts from the calcitonin receptor gene. Anusaksathien, O., Laplace, C., Li, X., Ren, Y., Peng, L., Goldring, S.R., Galson, D.L. J. Biol. Chem. (2001) [Pubmed]
  8. Properties of the nuclear P1 protein, a mammalian homologue of the yeast Mcm3 replication protein. Thömmes, P., Fett, R., Schray, B., Burkhart, R., Barnes, M., Kennedy, C., Brown, N.C., Knippers, R. Nucleic Acids Res. (1992) [Pubmed]
  9. Mouse pre-replicative complex proteins colocalise and interact with the centrosome. Stuermer, A., Hoehn, K., Faul, T., Auth, T., Brand, N., Kneissl, M., P??tter, V., Grummt, F. Eur. J. Cell Biol. (2007) [Pubmed]
  10. A murine replication protein accumulates temporarily in the heterochromatic regions of nuclei prior to initiation of DNA replication. Starborg, M., Brundell, E., Gell, K., Larsson, C., White, I., Daneholt, B., Höög, C. J. Cell. Sci. (1995) [Pubmed]
  11. A new family of 10 murine ovalbumin serpins includes two homologs of proteinase inhibitor 8 and two homologs of the granzyme B inhibitor (proteinase inhibitor 9). Sun, J., Ooms, L., Bird, C.H., Sutton, V.R., Trapani, J.A., Bird, P.I. J. Biol. Chem. (1997) [Pubmed]
  12. Differential Pax6 promoter activity and transcript expression during forebrain development. Anderson, T.R., Hedlund, E., Carpenter, E.M. Mech. Dev. (2002) [Pubmed]
  13. Developmental and regional expression of sodium channel isoform NaCh6 in the rat central nervous system. Schaller, K.L., Caldwell, J.H. J. Comp. Neurol. (2000) [Pubmed]
  14. Detection of beet yellows closterovirus methyltransferase-like and helicase-like proteins in vivo using monoclonal antibodies. Erokhina, T.N., Zinovkin, R.A., Vitushkina, M.V., Jelkmann, W., Agranovsky, A.A. J. Gen. Virol. (2000) [Pubmed]
  15. Ecto-alkaline phosphatase in NG108-15 cells : a key enzyme mediating P1 antagonist-sensitive ATP response. Ohkubo, S., Kimura, J., Matsuoka, I. Br. J. Pharmacol. (2000) [Pubmed]
  16. An SRLLR motif downstream of the scissile bond enhances enterokinase cleavage efficiency. Liew, O.W., Jenny Chong, P.C., Lim, Y.Z., Ang, C.X., Amy Lau, Y.C., Yandle, T.G., Brennan, S.O. Biochimie (2007) [Pubmed]
  17. Ciz1 promotes mammalian DNA replication. Coverley, D., Marr, J., Ainscough, J. J. Cell. Sci. (2005) [Pubmed]
  18. A novel promoter variant of the natriuretic peptide clearance receptor gene is associated with lower atrial natriuretic peptide and higher blood pressure in obese hypertensives. Sarzani, R., Dessì-Fulgheri, P., Salvi, F., Serenelli, M., Spagnolo, D., Cola, G., Pupita, M., Giantomassi, L., Rappelli, A. J. Hypertens. (1999) [Pubmed]
  19. Analysis of promoter and androgen regulatory sequences required for optimal transcription of the rat androgen-binding protein gene. Fenstermacher, D.A., Joseph, D.R. J. Androl. (1998) [Pubmed]
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