MCM3 explained

DNA replication licensing factor MCM3 is a protein that in humans is encoded by the MCM3 gene.^[1]

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 is a subunit of the protein complex that consists of MCM2-7. It has been shown to interact directly with MCM5/CDC46. This protein also interacts with, and thus is acetylated by MCM3AP, a chromatin-associated acetyltransferase. The acetylation of this protein inhibits the initiation of DNA replication and cell cycle progression.^[2]

Interactions

MCM3 has been shown to interact with:

• CDC45-related protein,
• CDC6,^{[3] [4]}
• DBF4,
  • MCM2 MCM3AP,^{[5] [6] [7]}
• MCM5,^[8]
• MCM7,^{[3] [9] [10]}
• ORC4L,^[11] and
• ORC5L.^[11]

See also

• Mini Chromosome Maintenance

Further reading

• Musahl C, Schulte D, Burkhart R, Knippers R . A human homologue of the yeast replication protein Cdc21. Interactions with other Mcm proteins . Eur. J. Biochem. . 230 . 3 . 1096–101 . 1995 . 7601140 . 10.1111/j.1432-1033.1995.tb20660.x .
• Schulte D, Burkhart R, Musahl C, Hu B, Schlatterer C, Hameister H, Knippers R . Expression, phosphorylation and nuclear localization of the human P1 protein, a homologue of the yeast Mcm 3 replication protein . J. Cell Sci. . 108 . 4 . 1381–9 . 1995 . 10.1242/jcs.108.4.1381 . 7615659 .
• Starborg M, Brundell E, Gell K, Larsson C, White I, Daneholt B, Höög C . A murine replication protein accumulates temporarily in the heterochromatic regions of nuclei prior to initiation of DNA replication . J. Cell Sci. . 108 . 3 . 927–34 . 1995 . 10.1242/jcs.108.3.927 . 7622621 .
• Burkhart R, Schulte D, Hu D, Musahl C, Göhring F, Knippers R . Interactions of human nuclear proteins P1Mcm3 and P1Cdc46 . Eur. J. Biochem. . 228 . 2 . 431–8 . 1995 . 7705359 . 10.1111/j.1432-1033.1995.tb20281.x .
• Kubota Y, Mimura S, Nishimoto S, Takisawa H, Nojima H . Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor . Cell . 81 . 4 . 601–9 . 1995 . 7758114 . 10.1016/0092-8674(95)90081-0 . 18797719 . free .
• Madine MA, Khoo CY, Mills AD, Laskey RA . MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells . Nature . 375 . 6530 . 421–4 . 1995 . 7760938 . 10.1038/375421a0 . 1995Natur.375..421M . 4316044 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Hu B, Burkhart R, Schulte D, Musahl C, Knippers R . The P1 family: a new class of nuclear mammalian proteins related to the yeast Mcm replication proteins . Nucleic Acids Res. . 21 . 23 . 5289–93 . 1994 . 8265339 . 310560 . 10.1093/nar/21.23.5289-a .
• Schulte D, Richter A, Burkhart R, Musahl C, Knippers R . Properties of the human nuclear protein p85Mcm. Expression, nuclear localization and interaction with other Mcm proteins . Eur. J. Biochem. . 235 . 1–2 . 144–51 . 1996 . 8631321 . 10.1111/j.1432-1033.1996.00144.x . free .
• 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 .
• Sato N, Arai K, Masai H . Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro phosphorylation of MCM subunits by a putative human homologue of Cdc7 . EMBO J. . 16 . 14 . 4340–51 . 1997 . 9250678 . 1170060 . 10.1093/emboj/16.14.4340 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Takei Y, Tsujimoto G . Identification of a novel MCM3-associated protein that facilitates MCM3 nuclear localization . J. Biol. Chem. . 273 . 35 . 22177–80 . 1998 . 9712829 . 10.1074/jbc.273.35.22177 . free .
• Zhang JJ, Zhao Y, Chait BT, Lathem WW, Ritzi M, Knippers R, Darnell JE . Ser727-dependent recruitment of MCM5 by Stat1alpha in IFN-gamma-induced transcriptional activation . EMBO J. . 17 . 23 . 6963–71 . 1999 . 9843502 . 1171044 . 10.1093/emboj/17.23.6963 .
• Yankulov K, Todorov I, Romanowski P, Licatalosi D, Cilli K, McCracken S, Laskey R, Bentley DL . MCM Proteins Are Associated with RNA Polymerase II Holoenzyme . Mol. Cell. Biol. . 19 . 9 . 6154–63 . 1999 . 10454562 . 84545 . 10.1128/MCB.19.9.6154.
• Fujita M, Yamada C, Goto H, Yokoyama N, Kuzushima K, Inagaki M, Tsurumi T . Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation . J. Biol. Chem. . 274 . 36 . 25927–32 . 1999 . 10464337 . 10.1074/jbc.274.36.25927 . free .
• Kuwahara K, Yoshida M, Kondo E, Sakata A, Watanabe Y, Abe E, Kouno Y, Tomiyasu S, Fujimura S, Tokuhisa T, Kimura H, Ezaki T, Sakaguchi N . A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication . Blood . 95 . 7 . 2321–8 . 2000 . 10733502 . 10.1182/blood.V95.7.2321.
• Hofmann Y, Becker J, Wright F, Avner ED, Mrug M, Guay-Woodford LM, Somlo S, Zerres K, Germino GG, Onuchic LF . Genomic structure of the gene for the human P1 protein (MCM3) and its exclusion as a candidate for autosomal recessive polycystic kidney disease . Eur. J. Hum. Genet. . 8 . 3 . 163–6 . 2000 . 10780780 . 10.1038/sj.ejhg.5200426 . free .
• Abe E, Kuwahara K, Yoshida M, Suzuki M, Terasaki H, Matsuo Y, Takahashi EI, Sakaguchi N . Structure, expression, and chromosomal localization of the human gene encoding a germinal center-associated nuclear protein (GANP) that associates with MCM3 involved in the initiation of DNA replication . Gene . 255 . 2 . 219–27 . 2000 . 11024281 . 10.1016/S0378-1119(00)00336-X .

Notes and References

1. Thömmes P, Fett R, Schray B, Burkhart R, Barnes M, Kennedy C, Brown NC, Knippers R . Properties of the nuclear P1 protein, a mammalian homologue of the yeast Mcm3 replication protein . Nucleic Acids Res . 20 . 5 . 1069–74 . April 1992 . 1549468 . 312092 . 10.1093/nar/20.5.1069 .
2. Web site: Entrez Gene: MCM3 MCM3 minichromosome maintenance deficient 3 (S. cerevisiae).
3. Fujita M, Yamada C, Goto H, Yokoyama N, Kuzushima K, Inagaki M, Tsurumi T . Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation . J. Biol. Chem. . 274 . 36 . 25927–32 . September 1999 . 10464337 . 10.1074/jbc.274.36.25927 . free .
4. Méndez J, Stillman B . Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis . Mol. Cell. Biol. . 20 . 22 . 8602–12 . November 2000 . 11046155 . 102165 . 10.1128/mcb.20.22.8602-8612.2000 .
5. Takei Y, Assenberg M, Tsujimoto G, Laskey R . The MCM3 acetylase MCM3AP inhibits initiation, but not elongation, of DNA replication via interaction with MCM3 . J. Biol. Chem. . 277 . 45 . 43121–5 . November 2002 . 12226073 . 10.1074/jbc.C200442200 . free .
6. Kuwahara K, Yoshida M, Kondo E, Sakata A, Watanabe Y, Abe E, Kouno Y, Tomiyasu S, Fujimura S, Tokuhisa T, Kimura H, Ezaki T, Sakaguchi N . A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication . Blood . 95 . 7 . 2321–8 . April 2000 . 10733502 . 10.1182/blood.V95.7.2321.
7. Takei Y, Tsujimoto G . Identification of a novel MCM3-associated protein that facilitates MCM3 nuclear localization . J. Biol. Chem. . 273 . 35 . 22177–80 . August 1998 . 9712829 . 10.1074/jbc.273.35.22177 . free .
8. 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 . March 2001 . 11248027 . 30602 . 10.1073/pnas.061487598 . 2001PNAS...98.3034D . free .
9. 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 . April 1997 . 9099751 . 10.1074/jbc.272.16.10928 . free .
10. Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T . Nuclear organization of DNA replication initiation proteins in mammalian cells . J. Biol. Chem. . 277 . 12 . 10354–61 . March 2002 . 11779870 . 10.1074/jbc.M111398200 . free .
11. 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 . March 2003 . 12614612 . 10.1016/s0022-2836(03)00079-2 .