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Published online 1 November 2004. doi:10.1083/jcb.200405102
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 3, 433-443
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Article

A cell sizer network involving Cln3 and Far1 controls entrance into S phase in the mitotic cycle of budding yeast

Lilia Alberghina, Riccardo L. Rossi, Lorenzo Querin, Valeria Wanke, and Marco Vanoni

Department of Biotechnology and Biosciences,Universiy of Milano-Bicocca, 20126 Milan, Italy

Correspondence to Lilia Alberghina: lilia.alberghina{at}unimib.it; or Marco Vanoni: marco.vanoni{at}unimib.it

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.

Abbreviations used in this paper: Cki, Cdk inhibitors; P, protein content; Ps, protein content per cell at the onset of DNA replication; SC, synthetic complete; SCD, SC medium with glucose; SCE, SC medium with ethanol.


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