“…Such studies using the well‐characterized E. coli oriC plasmids indicated that a significant number of the DnaA‐boxes and binding sites for architectural proteins were essential for origin activity (Asai et al , ; Woelker & Messer, ; Roth et al , ; Langer et al , ; McGarry et al , ). However, several laboratories subsequently showed that this plasmid system does not faithfully reflect oriC within its native environment and mutagenesis of the endogenous E. coli oriC has revealed that none of the protein binding sites is individually essential for origin function (Weigel et al , ; Stepankiw et al , ; Kaur et al , ; Noguchi et al , ; Sakiyama et al , ). Thus, despite isolation of a bacterial replication origin almost forty years ago, the minimal essential sequences that are necessary and sufficient to support a specific DnaA‐dependent unwinding mechanism remain unknown.…”