Fig. 1

Kinetic model of Clb/Cdk1 regulation and computational time courses of total Clb cyclins levels. a Network highlighting in red the sequential transcriptional activation of Clb cylins, thereby Clb/Cdk1 activities (k _A, k _B, k _C, and k _D). b Simulations of the network in Fig. 1a are carried out with standard values of parameters, as reported in Supplementary Text for details.¹² c–e Model variants were generated starting from the network in Fig. 1a by varying values of k _A (c), k _B (d), and k _C (e), as indicated on each simulation panel and described in the text. The model variants were implemented by ordinary differential equations, with the parameters used for the simulations having the same value among all variants (see Supplementary Text for model description and the full set of equations).¹² f–i Prediction and validation of the transcriptional regulation responsible for the delay between waves of Clb cyclins. The graphs report the time delay observed between maximum levels (peaks) of Clb cyclins for binary combinations between the minimal model—where Clb/Cdk1 complexes are connected via four transcriptional regulations—and two model variants, independently. f, g Time delay calculated for the left branch (only k _C active) between Clb5,6 and Clb3,4 (t _3,4−t _5,6) (f) and Clb3,4 and Clb1,2 (t _1,2−t _3,4) (g). h, i Time delay calculated for the right branch (only k _A and k _B active) between Clb5,6 and Clb3,4 (t _3,4−t _5,6) (h) and Clb3,4 and Clb1,2 (t _1,2−t _3,4) (i). Each parameter of the network may vary from its selected value to the same value multiplied for a random real value comprised between 0.1 and 10, as indicated on each simulation panel