The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

MCM5  -  MCM DNA helicase complex subunit MCM5

Saccharomyces cerevisiae S288c

Synonyms: BOB1, CDC46, Cell division control protein 46, L9328.1, Minichromosome maintenance protein 5, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

High impact information on CDC46

  • A family of related yeast replication proteins, MCM2, 3 and 5 (also called, after cell-division cycle, CDC46), resemble licensing factor, entering the nucleus only during mitosis [1].
  • Here, we show that the other genes, like CDC46, are all involved in an early step of DNA replication, possibly initiation of DNA synthesis [2].
  • The DNA sequence of the CDC46 gene indicates that the protein is a member of a new family of genes apparently required for DNA initiation, with family members now identified in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and mouse cells [2].
  • Subcellular localization of yeast CDC46 varies with the cell cycle [3].
  • We propose that the CDC46 protein, which is required for DNA replication, becomes mobilized quickly from the cytoplasm into the nucleus as mitosis is completed and persists there until the next round of division is initiated [3].

Biological context of CDC46

  • CDC45 genetically interacts with at least two members of the MCM (minichromosome maintenance) family of replication genes, CDC46 and CDC47, which are proposed to perform a role in restricting initiation of DNA replication to once per cell cycle [4].
  • CDC54 is a gene essential for initiation of DNA replication in Saccharomyces cerevisiae, and which is known to genetically interact with other regulators of the S-phase, including CDC46 [5].
  • Mcm3-1 contains a G246E mutation that diminishes the efficiency of replication initiation (Yan, H., Merchant, A. M., and Tye, B. K. (1993) Genes Dev. 7, 2149-2160) but not its interaction with Mcm5 or recruitment of the MCM2-7 complex to replication origin [6].
  • Molecular experiments revealed that the mcm5-bob1 mutation allows for constitutive loading of Cdc45p at early origins in arrested G1 phase cells when both kinases are inactive [7].
  • A model is proposed in which the Mcm5-bob1 protein assumes a unique molecular conformation without prior action by either kinase [7].

Associations of CDC46 with chemical compounds

  • When MCM5 cDNA was reintroduced into fresh TR9-7ER cells, numerous colonies that grow in the absence of tetracycline were formed [8].

Physical interactions of CDC46

  • Cdc45p assembles into a complex with Cdc46p/Mcm5p, is required for minichromosome maintenance, and is essential for chromosomal DNA replication [4].
  • The assembly of Cdc47p into complexes with Cdc46p does not appear to be cell cycle regulated, making it unlikely that these interactions per se are a rate-limiting step in the control of S phase [9].

Regulatory relationships of CDC46

  • Genetic experiments revealed that loss of either Clb5p or Clb2p cyclins suppresses the mcm5-bob1 mutation and prevents bypass [7].

Other interactions of CDC46

  • We characterize two mutations in CDC47 and CDC46 which arrest cells with unduplicated DNA as a result of single base substitutions [9].
  • Mcm3-10 contains a P118L substitution that compromises its interaction with Mcm5 and the recruitment of Mcm3 and Mcm7 to a replication origin [6].
  • These include the Saccharomyces cerevisiae MCM2 and MCM3 proteins, which are needed for the efficient function of certain replication origins, and S.cerevisiae CDC46, which is required for the initiation of chromosome replication [10].
  • Finally, activation of the DNA damage checkpoint and the resulting cell cycle delay is intact in cdc7Delta mcm5-bob1 cells, suggesting a direct role for CDC7 in DNA repair/damage tolerance [11].
  • Rereplication from origins requires both Cdc6p and Cdc46/Mcm5p, initiation proteins that had been thought to be inactivated by the Cdc28p kinase [12].

Analytical, diagnostic and therapeutic context of CDC46


  1. MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells. Madine, M.A., Khoo, C.Y., Mills, A.D., Laskey, R.A. Nature (1995) [Pubmed]
  2. A group of interacting yeast DNA replication genes. Hennessy, K.M., Lee, A., Chen, E., Botstein, D. Genes Dev. (1991) [Pubmed]
  3. Subcellular localization of yeast CDC46 varies with the cell cycle. Hennessy, K.M., Clark, C.D., Botstein, D. Genes Dev. (1990) [Pubmed]
  4. Cdc45p assembles into a complex with Cdc46p/Mcm5p, is required for minichromosome maintenance, and is essential for chromosomal DNA replication. Hopwood, B., Dalton, S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. Cdc54 belongs to the Cdc46/Mcm3 family of proteins which are essential for initiation of eukaryotic DNA replication. Whitebread, L.A., Dalton, S. Gene (1995) [Pubmed]
  6. Two mcm3 mutations affect different steps in the initiation of DNA replication. Lei, M., Cheng, I.H., Roberts, L.A., McAlear, M.A., Tye, B.K. J. Biol. Chem. (2002) [Pubmed]
  7. The mcm5-bob1 bypass of Cdc7p/Dbf4p in DNA replication depends on both Cdk1-independent and Cdk1-dependent steps in Saccharomyces cerevisiae. Sclafani, R.A., Tecklenburg, M., Pierce, A. Genetics (2002) [Pubmed]
  8. DNA Replication Licensing Factor Minichromosome Maintenance Deficient 5 Rescues p53-Mediated Growth Arrest. Agarwal, M.K., Amin, A.R., Agarwal, M.L. Cancer Res. (2007) [Pubmed]
  9. Characterization of Cdc47p-minichromosome maintenance complexes in Saccharomyces cerevisiae: identification of Cdc45p as a subunit. Dalton, S., Hopwood, B. Mol. Cell. Biol. (1997) [Pubmed]
  10. Fission yeast cdc21+ belongs to a family of proteins involved in an early step of chromosome replication. Coxon, A., Maundrell, K., Kearsey, S.E. Nucleic Acids Res. (1992) [Pubmed]
  11. CDC7/DBF4 functions in the translesion synthesis branch of the RAD6 epistasis group in Saccharomyces cerevisiae. Pessoa-Brandão, L., Sclafani, R.A. Genetics (2004) [Pubmed]
  12. CDC16 controls initiation at chromosome replication origins. Heichman, K.A., Roberts, J.M. Mol. Cell (1998) [Pubmed]
  13. Coding sequence and chromosome mapping of the human gene (CDC46) for replication protein hCdc46/Mcm5. Paul, R., Hu, B., Musahl, C., Hameister, H., Knippers, R. Cytogenet. Cell Genet. (1996) [Pubmed]
  14. Saccharomyces cerevisiae CSM1 gene encoding a protein influencing chromosome segregation in meiosis I interacts with elements of the DNA replication complex. Wysocka, M., Rytka, J., Kurlandzka, A. Exp. Cell Res. (2004) [Pubmed]
  15. The roles of the MCM, ORC, and Cdc6 proteins in determining the replication competence of chromatin in quiescent cells. Madine, M.A., Swietlik, M., Pelizon, C., Romanowski, P., Mills, A.D., Laskey, R.A. J. Struct. Biol. (2000) [Pubmed]
  16. Loss control of Mcm5 interaction with chromatin in cdc6-1 mutated in CDC-NTP motif. Feng, L., Hu, Y., Wang, B., Wu, L., Jong, A. DNA Cell Biol. (2000) [Pubmed]
WikiGenes - Universities