A cell sizer network involving Cln3 and Far1 controls entrance into S phase in the mitotic cycle of budding yeast.
Saccharomyces cerevisiae must reach a carbon source-modulated critical cell size, protein content per cell at the onset of DNA replication (Ps), in order to enter S phase. Cells grown in glucose are larger than cells grown in ethanol. Here, we show that an increased level of the cyclin-dependent inhibitor Far1 increases cell size, whereas far1 Delta cells start bud emergence and DNA replication at a smaller size than wild type. Cln3 Delta, far1 Delta, and strains overexpressing Far1 do not delay budding during an ethanol glucose shift-up as wild type does. Together, these findings indicate that Cln3 has to overcome Far1 to trigger Cln-Cdc28 activation, which then turns on SBF- and MBF-dependent transcription. We show that a second threshold is required together with the Cln3/Far1 threshold for carbon source modulation of Ps. A new molecular network accounting for the setting of Ps is proposed.
Alberghina
Lilia
L
Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy. lilia.alberghina@unimib.it
Rossi
Riccardo L
RL
Querin
Lorenzo
L
Wanke
Valeria
V
Vanoni
Marco
M
D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000502:physiology*; D048429:Cell Size; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins / Q000502:physiology*; D004261:DNA Replication; D000431:Ethanol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008938:Mitosis; D012097:Repressor Proteins / Q000502:physiology*; D016196:S Phase; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D004718:Saccharomycetales / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D014158:Transcription, Genetic
C079895:CLN3 protein, S cerevisiae; D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; C081353:FAR1 protein, S cerevisiae; D012097:Repressor Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000431:Ethanol; D017489:CDC28 Protein Kinase, S cerevisiae; D005947:Glucose