A cell sizer network involving Cln3 and Far 1 controls entrance into S phase in the mitotic cycle of budding yeast.

Saccharomyces cerevisiae must reach a carbon source-modulated critical cell size, protein con- tent 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 Fan increases cell size, whereas far 1δ cells start bud emergence and DNA replication at a smaller size than wild lype. Cln3δ, far 1δ, and strains overexpressing Fan1 do not delay budding during an ethanol glucose shift-up as wild type does. Together, these findings indicate that Cln3 has to overcome Fan 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 selling of Ps is proposed. [ABSTRACT FROM AUTHOR]