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Gene Review:

MCM4 - MCM DNA helicase complex subunit MCM4

Saccharomyces cerevisiae S288c

Synonyms: CDC54, Cell division control protein 54, DNA replication licensing factor MCM4, HCD21, YP9531.13, ...

Kearsey, S.E. et al., Whitebread, L.A. et al., Su, N.Y. et al., Labib, K. et al., Labib, K. et al., et al.

Kearsey, Montgomery, Labib, Lindner, Li, Cox,

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High impact information on CDC54

G1-phase and B-type cyclins exclude the DNA-replication factor Mcm4 from the nucleus [1].
Although origin firing can be triggered by the B-type cyclins only, both G1-phase and B-type cyclins cause exit of Mcm4 from the nucleus [1].
We have applied this method to the DNA replication factor mcm4/cdc21, and find that chromatin association occurs during anaphase B, significantly earlier than is the case in budding yeast [2].
Release of mcm4 from chromatin occurs during S phase and requires DNA replication [2].
Upon overexpressing cdc18, we show that mcm4 is required for re-replication of the genome in the absence of mitosis and is associated with chromatin in cells undergoing re-replication [2].

Biological context of CDC54

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 [3].
Cdc54 belongs to the Cdc46/Mcm3 family of proteins which are essential for initiation of eukaryotic DNA replication [3].
Consistent with the DNA replication defects, chromatin immunoprecipitation experiments revealed significantly lower levels of the replication factors Mcm4, Mcm7, and Cdc45 at replication origins in met30 mutants than in wild-type cells [4].
Later in meiosis, Mcm4 chromatin association is blocked between meiotic nuclear divisions, presumably accounting for the absence of a second round of DNA replication [5].
The encoded protein, termed PfMCM4, contains all conserved sequences in the MCM family and displays the highest homology to the Cdc54 (MCM4) of Saccharomyces cerevisiae [6].

Other interactions of CDC54

Comparison of Cdc54p to related proteins from other species revealed that it closely resembles cdc21p from Schizosaccharomyces pombe [3].
It is likely that pre-RCs contain heteromeric complexes of MCM2-7 proteins, since degradation of Mcm2, 3, 6, or 7 during G1-phase, after pre-RC formation, causes loss of Mcm4 from the nucleus [7].

Analytical, diagnostic and therapeutic context of CDC54

These toroidal structures are distinct from that of the Mcm4/6/7 hexamer, which was also examined by electron microscopy [8].

References

G1-phase and B-type cyclins exclude the DNA-replication factor Mcm4 from the nucleus. Labib, K., Diffley, J.F., Kearsey, S.E. Nat. Cell Biol. (1999) [Pubmed]
Chromatin binding of the fission yeast replication factor mcm4 occurs during anaphase and requires ORC and cdc18. Kearsey, S.E., Montgomery, S., Labib, K., Lindner, K. EMBO J. (2000) [Pubmed]
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]
The F-box protein Met30 is required for multiple steps in the budding yeast cell cycle. Su, N.Y., Flick, K., Kaiser, P. Mol. Cell. Biol. (2005) [Pubmed]
Essential role of MCM proteins in premeiotic DNA replication. Lindner, K., Gregán, J., Montgomery, S., Kearsey, S.E. Mol. Biol. Cell (2002) [Pubmed]
Identification of an MCM4 homologue expressed specifically in the sexual stage of Plasmodium falciparum. Li, J.L., Cox, L.S. Int. J. Parasitol. (2001) [Pubmed]
MCM2-7 proteins are essential components of prereplicative complexes that accumulate cooperatively in the nucleus during G1-phase and are required to establish, but not maintain, the S-phase checkpoint. Labib, K., Kearsey, S.E., Diffley, J.F. Mol. Biol. Cell (2001) [Pubmed]
Mammalian Mcm2/4/6/7 complex forms a toroidal structure. Yabuta, N., Kajimura, N., Mayanagi, K., Sato, M., Gotow, T., Uchiyama, Y., Ishimi, Y., Nojima, H. Genes Cells (2003) [Pubmed]

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AgaP_AGAP004956	Anopheles gambiae str. PEST
MCM4	Arabidopsis thaliana
AGOS_ADL026W	Ashbya gossypii ATCC 10895
MCM4	Bos taurus
mcm-4	Caenorhabditis elegans
MCM4	Canis lupus familiaris
mcm4	Danio rerio
dpa	Drosophila melanogaster
MCM4	Gallus gallus
MCM4	Homo sapiens
KLLA0C17512g	Kluyveromyces lactis NRRL Y-1140
MCM4	Macaca mulatta
MGG_09293	Magnaporthe oryzae 70-15
Mcm4	Mus musculus
NCU02539	Neurospora crassa OR74A
MCM4	Pan troglodytes
Mcm4	Rattus norvegicus
mcm4	Schizosaccharomyces pombe 972h-
mcm4	Xenopus (Silurana) tropicalis

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