The replisome, a protein complex that drives DNA replication, comprises multiple DNA polymerases. During replication, one polymerase synthesizes the leading strand continuously, while another synthesizes the lagging strand discontinuously, producing short transient segments known as Okazaki fragments and gaps between them. After the synthesis of each Okazaki fragment, the lagging-strand polymerase dissociates either spontaneously or upon collision with the preceding fragment; however, the relative contributions of these mechanisms remain unclear. Here, we develop a biophysical model of semidiscontinuous replication by incorporating the stochastic dynamics of the lagging-strand polymerase. By computing the Okazaki fragment and gap-size distributions, we show the significance of polymerase dissociation in shaping these statistics. Applying the model to the T4 bacteriophage and B. subtilis replisomes, we find that collisions with preceding Okazaki fragments predominantly trigger polymerase dissociation.

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• Biomolecular & subcellular processes
• DNA-protein interactions
• Genome organization
• Replication