Dissecting the control mechanisms for DNA replication and cell division in E. coli

Understanding how single E. coli cells coordinate the timing of cell division with genome replication would unlock a classic problem of biology, and open the way to address cell-cycle progression at the single-cell level. Several recent studies produced new data and proposed different models, based on the hypothesis that replication-segregation is the bottleneck process for cell division. However, due to the apparent contrast in both experimental results and proposed mechanisms, the emerging picture is fragmented and unclear. In this work, we re-evaluate jointly available data and models, and we show that, while each model contains useful insights, none of the proposed models, as well as generalizations based on the same assumptions, correctly describes all the correlation patterns observed in data. This analysis leads us to conclude that the assumption that replication is the bottleneck process for cell division is too restrictive. Instead, we propose that two concurrent cycles responsible for division and initiation of DNA replication together set the time of cell division. This framework correctly captures available data and allows us to select a nearly constant added size per origin between subsequent initiations as the most likely mechanism setting initiation of replication.