Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae.
In budding yeast G1 cells increase in cell mass until they reach a critical cell size, at which point (called Start) they enter S phase, bud and duplicate their spindle pole bodies. Activation of the Cdc28 protein kinase by G1-specific cyclins Cln1, Cln2 or Cln3 is necessary for all three Start events. Transcriptional activation of CLN1 and CLN2 by SBF and MBF transcription factors also requires an active Cln-Cdc28 kinase and it has therefore been proposed that the sudden accumulation of CLN1 and CLN2 transcripts during late G1 occurs via a positive feedback loop. We report that whereas Cln1 and Cln2 are required for the punctual execution of most, if not all, other Start-related events, they are not required for the punctual activation of SBF- or MBF-driven transcription. Cln3, on the other hand, is essential. By turning off cyclin B proteolysis and turning on proteolysis of the cyclin B-Cdc28 inhibitor p40SIC1, Cln1 and Cln2 kinases activate cyclin B-Cdc28 kinases and thereby trigger S phase. Thus the accumulation of Cln1 and Cln2 kinases which starts the yeast cell cycle is set in motion by prior activation of SBF- and MBF-mediated transcription by Cln3-Cdc28 kinase. This dissection of regulatory events during late G1 demands a rethinking of Start as a single process that causes cells to be committed to the mitotic cell cycle.
Dirick
L
L
Research Institute of Molecular Pathology, Vienna, Austria.
Böhm
T
T
Nasmyth
K
K
D017489:CDC28 Protein Kinase, S cerevisiae / Q000502:physiology*; D019926:Cyclin B; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology; D004352:Drug Resistance, Microbial; D005656:Fungal Proteins / Q000378:metabolism / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D000072235:Mating Factor; D008957:Models, Genetic; D010455:Peptides / Q000494:pharmacology; D010675:Pheromones / Q000494:pharmacology; D012331:RNA, Fungal / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D016196:S Phase / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
C093749:CLB2 protein, S cerevisiae; D019926:Cyclin B; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D005656:Fungal Proteins; D010455:Peptides; D010675:Pheromones; D012331:RNA, Fungal; D012333:RNA, Messenger; C081540:SBF protein, S cerevisiae; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000072235:Mating Factor; D017489:CDC28 Protein Kinase, S cerevisiae