Mathematical Modelling of DNA Replication Reveals a Trade-off between Coherence of Origin Activation and Robustness against Rereplication
Figure 7
Multisite phosphorylation of Sld2 functions supports coherent origin firing without rereplication.
(A) Effects of hypothetical single phosphorylation of Sic1 for its fast degradation: less coherent S-Cdk activation (upper panel) but unaffected kinetics of origin firing (lower panel; red curve, reference parameter set; black curves, other admissible parameter sets). (B) The effect of reducing the number of phosphorylation sites in Sld2 to a single site is more pronounced. Origin firing starts earlier and the number of rereplicating origins is increased (lower panel) for all parameter sets. (C) Number of rereplicating origins ρ, mean time to firing τ, duration of firing Δ, and the length of S phase computed for the reference parameter set (red curves in (A) and (B)). Mean values and standard deviations for all admissible parameter sets (black curves in (A) and (B)) are given in brackets. (D) A hypothetical reduction in the number of phosphorylation events required to activate Sld2 strongly affects origin firing (rereplicating origins ρ, firing duration Δ, mean time to firing τ). There is an additional effect of the reduction of required Sld3 phosphorylation steps (from two to one), whereas a reduction in the required Sic1 phosphorylation steps (from six to one) has no additional impact.