Budding yeast Cdc6p induces re-replication in fission yeast by inhibition of SCF(Pop)-mediated proteolysis.
In fission yeast, overexpression of the replication initiator protein Cdc18p induces re-replication, a phenotype characterized by continuous DNA synthesis in the absence of cell division. In contrast, overexpression of Cdc6p, the budding yeast homolog of Cdc18p, does not cause re-replication in S. cerevisiae. However, we have found that Cdc6p has the ability to induce rereplication in fission yeast. Cdc6p cannot functionally replace Cdc18p, but instead interferes with the proteolysis of both Cdc18p and Rum1p, the inhibitor of the protein kinase Cdc2p. This activity of Cdc6p is entirely contained within a short N-terminal peptide, which forms a tight complex with Cdc2p and the F-box/WD-repeat protein Sud1p/Pop2p, a component of the SCF(Pop) ubiquitin ligase in fission yeast. These interactions are mediated by two distinct regions within the N-terminal region of Cdc6p and depend on the integrity of its Cdc2p phosphorylation sites. The data suggest that disruption of re-replication control by overexpression of Cdc6p in fission yeast is a consequence of sequestration of Cdc2p and Pop2p, two factors involved in the negative regulation of Rum1p, Cdc18p and potentially other replication proteins.
Wolf
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Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115, USA. dwolf@hsph.harvard.edu
McKeon
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Jackson
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D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004261:DNA Replication; D005656:Fungal Proteins / Q000378:metabolism; D051548:Histone Acetyltransferases; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism*; D012260:Ribonucleases; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors / Q000378:metabolism*
C066503:CDC6 protein, S cerevisiae; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D012097:Repressor Proteins; C086077:Rum1 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C082462:cdc18 protein, S pombe; D051548:Histone Acetyltransferases; C086444:SPT10 protein, S cerevisiae; D016203:CDC2 Protein Kinase; D012260:Ribonucleases; C079009:POP2 protein, S cerevisiae