In silico Simulations of Perturbations: (A) Wild-type behaviour. (B) Expression of Dbf4 reduced to 10% of nominal. (C) Expression of Cdc6 reduced to 10% of nominal. (D) Total abundance of Cdt1 reduced to 10% of nominal. Perturbations of Cdc6 and Dbf4 had a significant impact on replicative efficiency, as evidence by a reduced abundance of activated replication forks (FORK). In contrast, a similar reduction in Cdt1 levels had much less impact.