Cell cycle regulation in Escherichia coli: from governing principles, checkpoints, and control variables to molecular...

All cells share the basic challenge of integrating the various processes that ensure their faithful replication. In most bacteria, this occurs without the dedicated regulatory machinery and additional layers of internal organization seen in eukaryotic cells. Despite this apparent reduction in complexity, bacterial replication is remarkably faithful and can be exceptionally fast. While spatiotemporal regulation of cell cycle processes is crucial for such efficient and reliable proliferation, many aspects of this currently remain elusive in bacteria. In this review, we focus on the cell cycle regulation of Escherichia coli, one of the best-studied bacterial models. We highlight how large-scale quantitative phenomenological studies have leveraged cellular variability to identify governing principles of cell cycle control in recent years. We discuss how these principles constrain the ongoing search for molecular mechanisms, examine the limitations of various approaches, and compare contradicting models and proposed molecular mechanisms.