Robustness of circadian rhythms with respect to molecular noise -- Data Supplement - Supporting Information -- Proceedings of the National Academy of Sciences

Supporting information for Gonze et al. (January 15, 2002) Proc. Natl. Acad. Sci. USA, 10.1073/pnas.022628299.

Supporting Figure 6 Fig. 6.
Scheme of the deterministic five-variable core model considered for circadian oscillations, with indication of parameters characterizing the different steps [Goldbeter, A. (1995) Proc. R. Soc. London Ser. B 261, 319–324 and Goldbeter, A. (1996) Biochemical Oscillations and Cellular Rhythms: The Molecular Bases of Periodic and Chaotic Behavior (Cambridge Univ. Press, Cambridge, U.K.)]. The model is based on the repression exerted by the nuclear form of a clock protein (P_N) on the transcription of its gene into mRNA (M_P). mRNA is synthetized in the nucleus and transferred to the cytosol, where it accumulates at a maximum rate v_s; there it is degraded by an enzyme of maximum rate v_m and Michaelis constant K_m. The rate of synthesis of the protein P₀, proportional to M_P, is characterized by an apparent first-order rate constant k_s. Parameters v_i and K_i (i = 1,...,4) denote the maximum rate(s) and Michaelis constant(s) of the kinase and phosphatase involved in the reversible phosphorylation of P₀ into P₁ and P₁ into P₂, respectively. The fully phosphorylated form P₂ is degraded by an enzyme of maximum rate v_d and Michaelis constant K_d and transported into the nucleus at a rate characterized by the apparent first-order rate constant k₁. Transport of the nuclear form of the clock protein (P_N) into the cytosol is characterized by the apparent first-order rate constant k₂. The negative feedback exerted by the nuclear clock protein on gene transcription is described by an equation of the Hill type, in which n denotes the degree of cooperativity and K_I denotes the threshold constant for repression (see Appendix, Kinetic Equations of the Deterministic Model).