Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs

摘要

The molecular players driving phase-specific cell cycle events. Linear cascade of the three Clb/Cdk1 complexes, and mutual inhibition between these and the Clb/Cdk1 inhibitor Sic1. Interactions among the Clb/Cdk1 complexes. Solid lines indicate (7) proven interactions, whereas dotted lines indicate (3) hypothetical interactions (see Supplementary Table ). Full interaction diagram for designs , , , , and of the minimal cell cycle network. The scheme illustrates the core interactions in all model designs presented in this work, i.e. black and red arrows for the basal and activatory regulations, respectively, and highlights the progressive changes to the core structure introduced in designs (blue, red cross, orange, and green, respectively). Dotted arrows indicate the Cln(/Cdk1)- and Clb(/Cdk1)-mediated phosphorylation of Sic1 in Clb/Cdk1/Sic1 ternary complexes, resulting in its degradation. The complex formation between Clb/Cdk1 complexes and Sic1 is indicated with the parameter, referring to the quasi-steady-state assumption introduced in (see Supplementary Information, Section 1.6.2), which should be taken to be the regular complex formation ( for formation, for dissociation) for designs . Model derivations are reported in Supplementary Information, Section 1, and details of the reactions and their experimental evidence are reported in Supplementary Table .