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.