Apc10 and Ste9/Srw1, two regulators of the APC-cyclosome, as well as the CDK inhibitor Rum1 are required for G1 cell-cycle arrest in fission yeast.
Many eukaryotic cells arrest the cell cycle at G1 phase upon nutrient deprivation. In fission yeast, during nitrogen starvation, cells divide twice and arrest at G1. We have isolated a novel type of sterile mutant, which undergoes one additional S phase upon starvation and, as a result, arrests at G2. Three loci (apc10, ste9/srw1 and rum1) were identified. The apc10 mutants, previously unidentified, show, in addition to sterility, temperature-sensitive growth with defects in chromosome segregation. apc10(+) is essential for viability, encodes a conserved protein (a homologue of budding yeast Apc10/Doc1) and is required for ubiquitination and degradation of mitotic B-type cyclins. Apc10 does not co-sediment with the 20S APC-cyclosome, a ubiquitin ligase for B-type cyclins, and in the apc10 mutant the 20S complex is intact, suggesting that it is a novel regulator for this complex. A subpopulation of Apc10 does co-immunoprecipitate with the anaphase-promoting complex (APC). A second gene, ste9(+)/srw1(+), encodes a member of the fizzy-related family, also regulators of the APC. Finally, Rum1 is a cyclin-dependent kinase (CDK) inhibitor which exists only in G1. The results suggest that dual downregulation of CDK, one via the APC and the other via the CDK inhibitor, is a universal mechanism that is used to arrest cell cycle progression at G1.
Kominami
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Laboratory of Cell Regulation, Imperial Cancer Research Fund, PO Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Seth-Smith
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Toda
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D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D019926:Cyclin B; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000235:genetics / Q000502:physiology; D004791:Enzyme Inhibitors; D005656:Fungal Proteins / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics*; D020043:Genes, Essential / Q000502:physiology; D005800:Genes, Fungal / Q000502:physiology; D005816:Genetic Complementation Test; D008025:Ligases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D016196:S Phase; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism
D018797:Cell Cycle Proteins; C080328:Cig2 protein, S pombe; D019926:Cyclin B; D016213:Cyclins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C086077:Rum1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D014452:Ubiquitins; C082462:cdc18 protein, S pombe; C113000:srw1 protein, S pombe; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D018844:Cyclin-Dependent Kinases; D008025:Ligases