In silico perturbations to the consensus model agree with reported in vivo cell cycle defects. (A) Wildtype behaviour. (B) Reduction of the rate of Dbf4-MCM association (k12) to 50% of the nominal value. (C) Reduction of the rate of Cdc45 interaction with the pre-RC (k13) to 50% of the nominal value. In both cases, a decrease in the abundance of the FORK species indicates a defect in DNA replication.