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

Alberghina L, Rossi RL, Querin L, Wanke V, Vanoni M - J. Cell Biol. (2004)

Bottom Line: 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.A new molecular network accounting for the setting of Ps is proposed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy. lilia.alberghina@unimib.it

ABSTRACT
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.

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Molecular blueprint of the network controlling the G1 to S transition in budding yeast. (A) Schematic representation of a molecular threshold: the antagonistic effect of an activator (cyclin, green) and an inhibitor (Cki, red) sets the threshold for the response (blue). (B) Effect of Far1 overexpression on the G1 to S transition execution (large arrows) in cells growing in ethanol, and (C) in cells growing in glucose. The Cln3/Far1 threshold (blue) is set by the level of Far1 (red line) received by newborn cells. The threshold is executed when Cln3 (green line), exceeds Far1 and is made irreversible by Far1 degradation (red dotted line). The second threshold (orange) is set by Sic1 degradation. (D) Model of a two threshold network for the control of the G1 to S transition.
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fig6: Molecular blueprint of the network controlling the G1 to S transition in budding yeast. (A) Schematic representation of a molecular threshold: the antagonistic effect of an activator (cyclin, green) and an inhibitor (Cki, red) sets the threshold for the response (blue). (B) Effect of Far1 overexpression on the G1 to S transition execution (large arrows) in cells growing in ethanol, and (C) in cells growing in glucose. The Cln3/Far1 threshold (blue) is set by the level of Far1 (red line) received by newborn cells. The threshold is executed when Cln3 (green line), exceeds Far1 and is made irreversible by Far1 degradation (red dotted line). The second threshold (orange) is set by Sic1 degradation. (D) Model of a two threshold network for the control of the G1 to S transition.

Mentions: The threshold mechanism is outlined in Fig. 6 A. During G1, Cln3 amount per cell increases proportionally to cell mass (Cross and Blake, 1993). The Cln3/Far1 threshold (blue) is set by the level of Far1 (red line) that is mostly endowed to the cell at the previous cell division and remains approximately constant in G1 cells. When the amount of Cln3 (green line), very likely localized in the nucleus (Edgington and Futcher, 2001; Miller and Cross, 2001), overcomes that of Far1 (red solid line), a first threshold is overcome. The threshold is made irreversible by Cln–Cdc28-primed Far1 degradation (red dotted line). The S-shaped, thick blue line indicates the response of the threshold.


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

Alberghina L, Rossi RL, Querin L, Wanke V, Vanoni M - J. Cell Biol. (2004)

Molecular blueprint of the network controlling the G1 to S transition in budding yeast. (A) Schematic representation of a molecular threshold: the antagonistic effect of an activator (cyclin, green) and an inhibitor (Cki, red) sets the threshold for the response (blue). (B) Effect of Far1 overexpression on the G1 to S transition execution (large arrows) in cells growing in ethanol, and (C) in cells growing in glucose. The Cln3/Far1 threshold (blue) is set by the level of Far1 (red line) received by newborn cells. The threshold is executed when Cln3 (green line), exceeds Far1 and is made irreversible by Far1 degradation (red dotted line). The second threshold (orange) is set by Sic1 degradation. (D) Model of a two threshold network for the control of the G1 to S transition.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172493&req=5

fig6: Molecular blueprint of the network controlling the G1 to S transition in budding yeast. (A) Schematic representation of a molecular threshold: the antagonistic effect of an activator (cyclin, green) and an inhibitor (Cki, red) sets the threshold for the response (blue). (B) Effect of Far1 overexpression on the G1 to S transition execution (large arrows) in cells growing in ethanol, and (C) in cells growing in glucose. The Cln3/Far1 threshold (blue) is set by the level of Far1 (red line) received by newborn cells. The threshold is executed when Cln3 (green line), exceeds Far1 and is made irreversible by Far1 degradation (red dotted line). The second threshold (orange) is set by Sic1 degradation. (D) Model of a two threshold network for the control of the G1 to S transition.
Mentions: The threshold mechanism is outlined in Fig. 6 A. During G1, Cln3 amount per cell increases proportionally to cell mass (Cross and Blake, 1993). The Cln3/Far1 threshold (blue) is set by the level of Far1 (red line) that is mostly endowed to the cell at the previous cell division and remains approximately constant in G1 cells. When the amount of Cln3 (green line), very likely localized in the nucleus (Edgington and Futcher, 2001; Miller and Cross, 2001), overcomes that of Far1 (red solid line), a first threshold is overcome. The threshold is made irreversible by Cln–Cdc28-primed Far1 degradation (red dotted line). The S-shaped, thick blue line indicates the response of the threshold.

Bottom Line: 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.A new molecular network accounting for the setting of Ps is proposed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy. lilia.alberghina@unimib.it

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus