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Fission yeast G2/M transition is regulated by a biochemical reaction networkswhich contains four components: Cdc13, Cdc2, Wee1, and Cdc25. This circuit ischaracterized by the ultrasensitive responses of Wee1 or Cdc25 to Cdc13/Cdc2activity, and the bistability of Cdc2 activation. Previous work has shown thatthis bistability is governed by phosphorylation energy. In this article, wedeveloped the kinetic model of this circuit and conducted further thermodynamicanalysis on the role of phosphorylation energy (&[Delta]G). We showed thatlevel &[Delta]G shapes the response curves of Wee1 or Cdc25 to Cdc2 and governsthe intrinsic noise level of Cdc2 activity. More importantly, the mutuallyantagonistic chemical fluxes around the PdP cycles in G2/M circuit were shownto act as a stabilizer of Cdc2 activity against &[Delta]G fluctuations. Theseresults suggests the fundamental role of free energy and chemical fluxes on thesensitivity, bistability and robustness of G2/M transition.

Phosphorylation potential and chemical fluxes govern the biological performance of multiple PdP cycles