Dissecting the Control Mechanisms for DNA Replication and Cell Division in E. coli

Abstract

Understanding the classic problem of how single E. coli cells coordinate cell division with genome replication would open the way to addressing cell-cycle progression at the single-cell level. Recent studies produced new data, but the contrast in their conclusions and proposed mechanisms makes the emerging picture fragmented and unclear. Here, we re-evaluate available data and models, including generalizations based on the same assumptions. We show that although they provide useful insights, none of the proposed models captures all correlation patterns observed in data. We 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 set the time of cell division. This framework allows us to select a nearly constant added size per origin between subsequent initiations as the most likely mechanism setting initiation of replication. The current paradigm assumes that E. coli cell division occurs a fixed time after DNA replication, but recent single-cell studies reached contrasting conclusions on this. By model-guided data analysis, Micali et al. falsify the classic assumption and test mechanistic scenarios for concurrent processes competing to determine cell division.