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Gene Review

cdc18  -  MCM loader

Schizosaccharomyces pombe 972h-

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High impact information on cdc18

  • We show here that overexpressing cdc18 is able to bring about repeated rounds of DNA synthesis in the absence of mitosis and of continuing protein synthesis [1].
  • The level of the cdc18-encoded protein p65cdc18 is periodic in the cell cycle, peaking at the G1 to S phase transition, and p65cdc18 is located in the nucleus when cdc18 is overexpressed [1].
  • Conversely, deletion of ruml+ increases the severity of the cdc18 mutant phenotype, resulting in inappropriate cell division and a rapid loss of viability [2].
  • Chromatin binding of the fission yeast replication factor mcm4 occurs during anaphase and requires ORC and cdc18 [3].
  • We find that transcription of cdc18, together with the transcription of other cdc10p/res1p targets, is first initiated as cells enter mitosis and continues even in cells arrested in mitosis with highly condensed chromatin [4].

Biological context of cdc18


Regulatory relationships of cdc18


Other interactions of cdc18

  • We propose that cdc18p is central to the molecular mechanism co-ordinating S phase and M phase in concert with changes in activity of the master cell cycle regulator, the cdc2 protein kinase [11].
  • This model was examined by induction of overreplication of the genome by overexpression of rum1p or cdc18p [12].
  • These have been characterised physiologically, and 6 of the genes (cdc 17, 20, 21, 22, 23, 24) were found to be required for DNA replication, 2 for mitosis (cdc 27, 28), and 2 (cdc 18, 19), could not be unambiguously assigned to either DNA replication or mitosis but were definitely required for one or the other [13].


  1. p65cdc18 plays a major role controlling the initiation of DNA replication in fission yeast. Nishitani, H., Nurse, P. Cell (1995) [Pubmed]
  2. Rum1 and Cdc18 link inhibition of cyclin-dependent kinase to the initiation of DNA replication in Schizosaccharomyces pombe. Jallepalli, P.V., Kelly, T.J. Genes Dev. (1996) [Pubmed]
  3. 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]
  4. Cdc18 transcription and proteolysis couple S phase to passage through mitosis. Baum, B., Nishitani, H., Yanow, S., Nurse, P. EMBO J. (1998) [Pubmed]
  5. DNA polymerase alpha, a component of the replication initiation complex, is essential for the checkpoint coupling S phase to mitosis in fission yeast. D'Urso, G., Grallert, B., Nurse, P. J. Cell. Sci. (1995) [Pubmed]
  6. The role of nucleotide binding and hydrolysis in the function of the fission yeast cdc18(+) gene product. DeRyckere, D., Smith, C.L., Martin, G.S. Genetics (1999) [Pubmed]
  7. DNA polymerase delta is required for the replication feedback control of cell cycle progression in Schizosaccharomyces pombe. Francesconi, S., De Recondo, A.M., Baldacci, G. Mol. Gen. Genet. (1995) [Pubmed]
  8. The regulation of competence to replicate in meiosis by Cdc6 is conserved during evolution. Lemaître, J.M., Bocquet, S., Terret, M.E., Namdar, M., Aït-Ahmed, O., Kearsey, S., Verlhac, M.H., Méchali, M. Mol. Reprod. Dev. (2004) [Pubmed]
  9. DNA sequencing and analysis of a 67.4 kb region from the right arm of Schizosaccharomyces pombe chromosome II reveals 28 open reading frames including the genes his5, pol5, ppa2, rip1, rpb8 and skb1. Xiang, Z., Lyne, M.H., Wood, V., Rajandream, M.A., Barrell, B.G., Aves, S.J. Yeast (1999) [Pubmed]
  10. Cdc18p can block mitosis by two independent mechanisms. Greenwood, E., Nishitani, H., Nurse, P. J. Cell. Sci. (1998) [Pubmed]
  11. The cdc18 protein initiates DNA replication in fission yeast. Nishitani, H., Nurse, P. Progress in cell cycle research. (1997) [Pubmed]
  12. Spindle pole body duplication in fission yeast occurs at the G1/S boundary but maturation is blocked until exit from S by an event downstream of cdc10+. Uzawa, S., Li, F., Jin, Y., McDonald, K.L., Braunfeld, M.B., Agard, D.A., Cande, W.Z. Mol. Biol. Cell (2004) [Pubmed]
  13. Cell division cycle mutants altered in DNA replication and mitosis in the fission yeast Schizosaccharomyces pombe. Nasmyth, K., Nurse, P. Mol. Gen. Genet. (1981) [Pubmed]
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