Abstract
Living cells proliferate by completing and coordinating two cycles, a division cycle controlling cell size and a DNA replication cycle controlling the number of chromosomal copies. It remains unclear how bacteria such as Escherichia coli tightly coordinate those two cycles across a wide range of growth conditions. Here, we used time-lapse microscopy in combination with microfluidics to measure growth, division and replication in single E. coli cells in both slow and fast growth conditions. To compare different phenomenological cell cycle models, we introduce a statistical framework assessing their ability to capture the correlation structure observed in the data. In combination with stochastic simulations, our data indicate that the cell cycle is driven from one initiation event to the next rather than from birth to division and is controlled by two adder mechanisms: the added volume since the last initiation event determines the timing of both the next division and replication initiation events.
Highlights
Across all domains of life, cell proliferation requires that the chromosome replication and cell division cycles are coordinated to ensure that every new cell receives one copy of the genetic material
In the specific case of E. coli that we study here, it has long been known that growth rate, cell size, and replication initiation are coordinated such that the average number of replication origins per unit of cellular volume is approximately constant across conditions (Donachie, 1968) or that cellular volume grows approximately exponentially with growth rate (Taheri-Araghi et al, 2017)
The replication cycle was monitored by detecting initiation as the duplication of an oriC proximal FROS tagged locus imaged by fluorescence microscopy (Figure 1A)
Summary
Across all domains of life, cell proliferation requires that the chromosome replication and cell division cycles are coordinated to ensure that every new cell receives one copy of the genetic material. While in eukaryotes this coordination is implemented by a dedicated regulatory system in which genome replication and division occur in well-separated stages, no such system has been found in most bacteria. This suggests that the molecular events that control replication initiation and division might be coordinated more directly in bacteria, through molecular interactions that are yet to be elucidated. Several models have been proposed over the last decades to explain such observations (for a review and a historical perspective see for example Willis and Huang, 2017), so far direct validation of these models has been lacking, due to a large extent to the lack of quantitative measurements of cell cycles parameters in large samples with single-cell resolution
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