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 G 1 phase of the cell cycle. Here we present a mathematical model of the basic molecular mechanism controlling the G 1 /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 G 1 /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 G 1 cells. Cell cycle progression and transcriptional analyses of a Whi5 phosphomimetic mutant verify the model prediction that coherent transcription of the G 1 /S regulon and ensuing G 1 /S transition requires full phosphorylation of Whi5 functional sites.

Palumbo, P., Vanoni, M., Cusimano, V., Busti, S., Marano, F., Manes, C., et al. (2016). Whi5 phosphorylation embedded in the G 1 /S network dynamically controls critical cell size and cell fate. NATURE COMMUNICATIONS, 7 [10.1038/ncomms11372].

Whi5 phosphorylation embedded in the G 1 /S network dynamically controls critical cell size and cell fate

Palumbo, P
Co-primo
;
VANONI, MARCO ERCOLE
Co-primo
;
BUSTI, STEFANO;MARANO, FRANCESCA;ALBERGHINA, LILIA
2016

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 G 1 phase of the cell cycle. Here we present a mathematical model of the basic molecular mechanism controlling the G 1 /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 G 1 /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 G 1 cells. Cell cycle progression and transcriptional analyses of a Whi5 phosphomimetic mutant verify the model prediction that coherent transcription of the G 1 /S regulon and ensuing G 1 /S transition requires full phosphorylation of Whi5 functional sites.
Articolo in rivista - Articolo scientifico
CDC28 Protein Kinase; Cell Size; Cyclins; G1 Phase Cell Cycle Checkpoints; Mutation; Phosphorylation; Regulon; Repressor Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Transcription, Genetic; Gene Expression Regulation, Fungal; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all)
English
2016
7
11372
partially_open
Palumbo, P., Vanoni, M., Cusimano, V., Busti, S., Marano, F., Manes, C., et al. (2016). Whi5 phosphorylation embedded in the G 1 /S network dynamically controls critical cell size and cell fate. NATURE COMMUNICATIONS, 7 [10.1038/ncomms11372].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/140788
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