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Whi5 phosphorylation embedded in the G1/S network dynamically controls critical cell size and cell fate

Pasquale Palumbo (), Marco Vanoni, Valerio Cusimano, Stefano Busti, Francesca Marano, Costanzo Manes and Lilia Alberghina ()
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Pasquale Palumbo: SYSBIO.IT Center for Systems Biology
Marco Vanoni: SYSBIO.IT Center for Systems Biology
Valerio Cusimano: SYSBIO.IT Center for Systems Biology
Stefano Busti: SYSBIO.IT Center for Systems Biology
Francesca Marano: SYSBIO.IT Center for Systems Biology
Costanzo Manes: CNR-IASI, Italian National Research Council - Institute for Systems Analysis and Computer Science, Via dei Taurini 19
Lilia Alberghina: SYSBIO.IT Center for Systems Biology

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract In budding yeast, overcoming of a critical size to enter S phase and the mitosis/mating switch—two central cell fate events—take place in the G1 phase of the cell cycle. Here we present a mathematical model of the basic molecular mechanism controlling the G1/S transition, whose major regulatory feature is multisite phosphorylation of nuclear Whi5. Cln3–Cdk1, whose nuclear amount is proportional to cell size, and then Cln1,2–Cdk1, randomly phosphorylate both decoy and functional Whi5 sites. Full phosphorylation of functional sites releases Whi5 inhibitory activity, activating G1/S transcription. Simulation analysis shows that this mechanism ensures coherent release of Whi5 inhibitory action and accounts for many experimentally observed properties of mitotically growing or conjugating G1 cells. Cell cycle progression and transcriptional analyses of a Whi5 phosphomimetic mutant verify the model prediction that coherent transcription of the G1/S regulon and ensuing G1/S transition requires full phosphorylation of Whi5 functional sites.

Date: 2016
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DOI: 10.1038/ncomms11372

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