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Gene Review

MCM1  -  Mcm1p

Saccharomyces cerevisiae S288c

Synonyms: FUN80, GRM/PRTF protein, Pheromone receptor transcription factor, YM9532.08, YMR043W
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High impact information on MCM1

  • Its recruitment depends on a permanent protein-DNA complex consisting of the MADS box protein, Mcm1, and a recently identified partner Fkh2, a forkhead/winged helix related transcription factor [1].
  • The alpha 2-Mcm1 complex in turn recruits Ssn6 and Tup1 to the operator, and we believe that these latter two proteins are responsible for the transcriptional repression [2].
  • DNA-binding repressor proteins mediate regulation of yeast genes by cell type (Mcm1/alpha 2 and a1/alpha 2), glucose (Mig1) and oxygen (Rox1) (refs 1-4 respectively) [3].
  • Furthermore, we show that like p62TCF, Elk-1 forms complexes with the yeast SRF-homologue MCM1 but not with yeast ARG80 [4].
  • The inositol 1,4,5-trisphosphate kinase of this pathway in Saccharomyces cerevisiae, designated Ipk2, was found to be identical to Arg82, a regulator of the transcriptional complex ArgR-Mcm1 [5].

Biological context of MCM1


Anatomical context of MCM1

  • We speculate that MCM1 coordinates decisions about cell cycle progression with changes in cell wall integrity and metabolic activity [6].
  • Bound Mcm1 is resistant to extraction by nucleases, salt, and non-ionic detergent, but can be released by 5 M urea, suggesting that Mcm1 binds to a yeast equivalent of the nuclear pore complex-lamina fraction of higher eukaryotes [9].
  • Mcm1 was imported into the oocyte nucleus indicating that the machinery for nuclear transport is conserved from yeast to higher eukaryotes [10].

Associations of MCM1 with chemical compounds

  • Genetic evidence for a role for MCM1 in the regulation of arginine metabolism in Saccharomyces cerevisiae [11].
  • The MCM1 gene product is a protein of 286 amino acid residues and contains an unusual region in which 19 out of 20 residues are either aspartic or glutamic acid, followed by a series of glutamine tracts [8].
  • We also show that the AF-2 domain, although inactive at simple promoters on its own in yeast, can enhance transcription by the MCM1 activator in hormone-dependent manner, consistent with its having a role in activation as well as repression in the native ER [12].
  • Galactose-induced overexpression of MCM1 leads to rapid growth arrest at the G1 or S cell cycle stages, with many morphologically-abnormal cells [13].
  • Synthesis of inositol 1,4,5,6-tetrakisphosphate, but not IP6, was required for gene regulation through ArgR-Mcm1 [5].

Physical interactions of MCM1

  • Our in vitro binding experiments confirm the presence of MCM1 in the protein complex interacting with the promoters of the catabolic CAR1 and CAR2 genes [11].
  • The previously unidentified MCM1 binding site in the essential PMA1 gene is required for expression of a PMA1:lacZ fusion gene, providing evidence that one site is functionally important [6].
  • The PIS1 promoter includes sequences (MCEs) that bind the Mcm1 protein [7].
  • Analyses of these complexes by DNase I footprinting demonstrate that the PRTF binding site is confined to the palindromic P-box sequence in the case of the STE3 UAS, but extends symmetrically from this central region to cover 28 bp for the STE2 UAS [14].
  • At mating-gene promoters, MCM1 binds with coactivators or repressors such as STE12, alpha 1, or alpha 2 [15].

Regulatory relationships of MCM1

  • We provide evidence that the replication defect of mcm1 mutants can be suppressed by ectopic CDC6 transcription [16].
  • SLN1 also activates an MCM1-dependent reporter gene, P-lacZ, but this function is independent of Ssk1p [17].
  • Ste12 and Mcm1 regulate cell cycle-dependent transcription of FAR1 [18].
  • Our results suggest that SPT13 has a role in the negative control of MCM1 activity that is likely to be posttranslational [19].
  • We discuss the possibility that the CLB2 gene is coregulated with other genes known to be regulated with the same periodicity and suggest that Mcm1 and the ternary complex factor may coordinately regulate several other G2-regulated transcripts [20].

Other interactions of MCM1

  • However, constitutive CLB2 expression does not suppress the mitotic defect, and therefore other essential activities required for the G2-to-M transition must also depend on Mcm1 function [21].
  • The arrest phenotype of Mcm1-depleted cells is consistent with low levels of Clb1 and Clb2 kinase [21].
  • MCM1 has striking homology to ARG80, a regulatory gene of the arginine metabolic pathway located about 700 base-pairs upstream from MCM1 [8].
  • The homeodomian protein alpha 2, together with MCM1, recruits two general transcriptional repressors, SSN6 and TUP1, to the promoters of a-specific genes [22].
  • In the absence of both MCM1 and STE12 functions, no residual expression was observed [23].

Analytical, diagnostic and therapeutic context of MCM1

  • We show that in gel retardation assays, MCM1 recruits both ternary complex factors whereas SRF interacts only with p62TCF [24].
  • The structure of a complex containing the homeodomain repressor protein MATalpha2 and the MADS-box transcription factor MCM1 bound to DNA has been determined by X-ray crystallography at 2.25 A resolution [25].
  • Crystallization of the yeast MATalpha2/MCM1/DNA ternary complex: general methods and principles for protein/DNA cocrystallization [26].
  • Gel filtration experiments indicate that the ECB-specific DNA binding complex is over 200 kDa in size and includes Mcm1 and at least one additional protein [27].
  • Chromatin immunoprecipitations show that Mcm1 binds in vivo to ECB elements throughout the cell cycle and that binding is sensitive to carbon source changes [27].


  1. Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters. Koranda, M., Schleiffer, A., Endler, L., Ammerer, G. Nature (2000) [Pubmed]
  2. Transcriptional repression directed by the yeast alpha 2 protein in vitro. Herschbach, B.M., Arnaud, M.B., Johnson, A.D. Nature (1994) [Pubmed]
  3. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Tzamarias, D., Struhl, K. Nature (1994) [Pubmed]
  4. Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Hipskind, R.A., Rao, V.N., Mueller, C.G., Reddy, E.S., Nordheim, A. Nature (1991) [Pubmed]
  5. A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Odom, A.R., Stahlberg, A., Wente, S.R., York, J.D. Science (2000) [Pubmed]
  6. A library of yeast genomic MCM1 binding sites contains genes involved in cell cycle control, cell wall and membrane structure, and metabolism. Kuo, M.H., Grayhack, E. Mol. Cell. Biol. (1994) [Pubmed]
  7. Carbon source regulation of PIS1 gene expression in Saccharomyces cerevisiae involves the MCM1 gene and the two-component regulatory gene, SLN1. Anderson, M.S., Lopes, J.M. J. Biol. Chem. (1996) [Pubmed]
  8. Saccharomyces cerevisiae protein involved in plasmid maintenance is necessary for mating of MAT alpha cells. Passmore, S., Maine, G.T., Elble, R., Christ, C., Tye, B.K. J. Mol. Biol. (1988) [Pubmed]
  9. Nuclear import substrates compete for a limited number of binding sites. Evidence for different classes of yeast nuclear import receptors. Garcia-Bustos, J.F., Wagner, P., Hall, M.N. J. Biol. Chem. (1991) [Pubmed]
  10. Nuclear protein transport is functionally conserved between yeast and higher eukaryotes. Wagner, P., Hall, M.N. FEBS Lett. (1993) [Pubmed]
  11. Genetic evidence for a role for MCM1 in the regulation of arginine metabolism in Saccharomyces cerevisiae. Messenguy, F., Dubois, E. Mol. Cell. Biol. (1993) [Pubmed]
  12. Mutations in the AF-2/hormone-binding domain of the chimeric activator GAL4.estrogen receptor.VP16 inhibit hormone-dependent transcriptional activation and chromatin remodeling in yeast. Stafford, G.A., Morse, R.H. J. Biol. Chem. (1998) [Pubmed]
  13. An efficient method to isolate yeast genes causing overexpression-mediated growth arrest. Espinet, C., de la Torre, M.A., Aldea, M., Herrero, E. Yeast (1995) [Pubmed]
  14. Interactions of purified transcription factors: binding of yeast MAT alpha 1 and PRTF to cell type-specific, upstream activating sequences. Tan, S., Ammerer, G., Richmond, T.J. EMBO J. (1988) [Pubmed]
  15. MCM1 binds to a transcriptional control element in Ty1. Errede, B. Mol. Cell. Biol. (1993) [Pubmed]
  16. A novel Mcm1-dependent element in the SWI4, CLN3, CDC6, and CDC47 promoters activates M/G1-specific transcription. McInerny, C.J., Partridge, J.F., Mikesell, G.E., Creemer, D.P., Breeden, L.L. Genes Dev. (1997) [Pubmed]
  17. The yeast histidine protein kinase, Sln1p, mediates phosphotransfer to two response regulators, Ssk1p and Skn7p. Li, S., Ault, A., Malone, C.L., Raitt, D., Dean, S., Johnston, L.H., Deschenes, R.J., Fassler, J.S. EMBO J. (1998) [Pubmed]
  18. Ste12 and Mcm1 regulate cell cycle-dependent transcription of FAR1. Oehlen, L.J., McKinney, J.D., Cross, F.R. Mol. Cell. Biol. (1996) [Pubmed]
  19. SPT13 (GAL11) of Saccharomyces cerevisiae negatively regulates activity of the MCM1 transcription factor in Ty1 elements. Yu, G., Fassler, J.S. Mol. Cell. Biol. (1993) [Pubmed]
  20. Cell cycle-regulated transcription of the CLB2 gene is dependent on Mcm1 and a ternary complex factor. Maher, M., Cong, F., Kindelberger, D., Nasmyth, K., Dalton, S. Mol. Cell. Biol. (1995) [Pubmed]
  21. Mcm1 is required to coordinate G2-specific transcription in Saccharomyces cerevisiae. Althoefer, H., Schleiffer, A., Wassmann, K., Nordheim, A., Ammerer, G. Mol. Cell. Biol. (1995) [Pubmed]
  22. Identification of genes required for alpha 2 repression in Saccharomyces cerevisiae. Wahi, M., Johnson, A.D. Genetics (1995) [Pubmed]
  23. Relative contributions of MCM1 and STE12 to transcriptional activation of a- and alpha-specific genes from Saccharomyces cerevisiae. Hwang-Shum, J.J., Hagen, D.C., Jarvis, E.E., Westby, C.A., Sprague, G.F. Mol. Gen. Genet. (1991) [Pubmed]
  24. A protein domain conserved between yeast MCM1 and human SRF directs ternary complex formation. Mueller, C.G., Nordheim, A. EMBO J. (1991) [Pubmed]
  25. Crystal structure of the yeast MATalpha2/MCM1/DNA ternary complex. Tan, S., Richmond, T.J. Nature (1998) [Pubmed]
  26. Crystallization of the yeast MATalpha2/MCM1/DNA ternary complex: general methods and principles for protein/DNA cocrystallization. Tan, S., Hunziker, Y., Pellegrini, L., Richmond, T.J. J. Mol. Biol. (2000) [Pubmed]
  27. Characterization of the ECB binding complex responsible for the M/G(1)-specific transcription of CLN3 and SWI4. Mai, B., Miles, S., Breeden, L.L. Mol. Cell. Biol. (2002) [Pubmed]
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