||Replication initiates once DnaA accumulates at the replication origin, exposing a single-stranded DNA template to DNA polymerase. First, 7 DnaA molecules cooperatively accumulate at each of 4 high affinity boxes near the replication origin. Second, DnaA disrupts the double helix structure of DNA, exposing a region of single-stranded DNA. Third, two DNA polymerases bind the single-stranded region, and begin bidirectional leading strand replication. Next, lagging strand synthesis begins, and lagging strand Okazaki fragments are ligated by DNA ligase. Finally, replication completes when both polymerases reach the replication terminus.
Replication initiation is modeled as the stochastic binding and release of DnaA molecules to the genome's 2297 DnaA boxes. DNA polymerization is modeled similar to transcription and translation; nucleotides and energy are distributed among actively polymerizing leading and lagging strands. DNA ligation proceeds subject to the availability of DNA ligase and its cofactor NAD.