Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae

EMBO J. 1995 Oct 2;14(19):4803-13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC28 Protein Kinase, S cerevisiae / physiology*
  • Cyclin B*
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclins / genetics
  • Cyclins / metabolism
  • Cyclins / physiology*
  • DNA Replication / physiology
  • Drug Resistance, Microbial
  • Fungal Proteins / metabolism
  • Fungal Proteins / physiology*
  • G1 Phase / physiology*
  • Gene Expression Regulation, Fungal / physiology
  • Mating Factor
  • Models, Genetic
  • Peptides / pharmacology
  • Pheromones / pharmacology
  • RNA, Fungal / biosynthesis
  • RNA, Messenger / biosynthesis
  • S Phase / physiology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors / physiology
  • Transcription, Genetic

Substances

  • CLB2 protein, S cerevisiae
  • Cyclin B
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclins
  • Fungal Proteins
  • Peptides
  • Pheromones
  • RNA, Fungal
  • RNA, Messenger
  • SBF protein, S cerevisiae
  • SIC1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Mating Factor
  • CDC28 Protein Kinase, S cerevisiae