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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, 319324 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 (PN) on the transcription of its gene into mRNA (MP). mRNA is synthetized in the nucleus and transferred to the cytosol, where it accumulates at a maximum rate vs; there it is degraded by an enzyme of maximum rate vm and Michaelis constant Km. The rate of synthesis of the protein P0, proportional to MP, is characterized by an apparent first-order rate constant ks. Parameters vi and Ki (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 vd and Michaelis constant Kd 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 (PN) 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 KI denotes the threshold constant for repression (see Appendix, Kinetic Equations of the Deterministic Model).


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