Modeling of DNA replication in rapidly growing bacteria with one and two replication origins

Abstract

AbstractIn rapidly growing bacteria initiation of DNA replication occurs at intervals shorter than the time required for completing genome duplication, leading to overlapping rounds of replication. We propose a mathematical model of DNA replication defined by the periodicity of replication initiation. Our model predicts that a steeper gradient of the replication profile is to be expected in origin proximal regions due to the overlapping rounds of synthesis. By comparing our model with experimental data from a strain with an additional replication origin, we predict defined alterations to replication parameters: (i) a reduced fork velocity when there were twice as many forks as normal; (ii) a slower fork speed if forks move in a direction opposite to normal, in line with head-on replication-transcription collisions being a major obstacle for fork progression; (iii) slower cell doubling for a double origin strain compared to wild-type cells; and (iv) potentially an earlier initiation of replication at the ectopic origin than at the natural origin, which, however, does not a˙ect the overall time required to complete synthesis.