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

• Genetic analysis in the yeast Schizosaccharomyces pombe has shown that three genes cdc18, cut5, and cdt1, are essential for DNA synthesis and also for the checkpoint control that couples completion of DNA replication to the onset of mitosis [5].
• The role of nucleotide binding and hydrolysis in the function of the fission yeast cdc18(+) gene product [6].
• Thermosensitive mutations in the DNA polymerase delta, cdc18 or cdc20 genes lead cells to arrest in the S phase of the cell cycle [7].
• We also show that, contrary to eukaryotic metazoans, in S. pombe cdc18 (the S. pombe CDC6 homologue), CDC6 protein synthesis is down regulated during meiosis [8].
• 67 393 bp of contiguous DNA located between markers cdc18 and cdc14 on the right arm of fission yeast chromosome II has been sequenced as part of the European Union Schizosaccharomyces pombe genome sequencing project [9].

Regulatory relationships of cdc18

• The N terminus of cdc18p can also block mitosis but does so in the absence of the DNA replication checkpoint genes and the wee1p/mik1p kinases therefore acting downstream of these genes [10].

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].

References