Effect of Replication Fork Dynamics on Escherichia coli Cell Size
release_cshlyulj2zesnevmqk5rjthdsi
by
Chaitanya A. Athale
2017
Abstract
The variability in cell size of an isogenic population of Escherichia coli
has been widely reported in experiment. The probability density function (PDF)
of cell lengths has been variously described by exponential and lognormal
functions. While temperature, population density and growth rate have all been
shown to affect E. coli cell size distributions, and recent models have
validated a link between growth rate and cell size through DNA replication,
cell size variability is thought to emerge from growth rate variability. A
mechanistic link that could distinguish the source of stochasticity, could
improve our understanding of cell size regulation. Here, we have developed a
population dynamics model of individual cell division based on the BCD, birth,
chromosome replication and division model, with DNA replication based on the
Cooper and Helmstetter (CH) multi-fork replication. In our model, stochasticity
in the model arises solely from the dynamics of DNA replication forks. We model
the forks as two-state systems: stalled and recovered. Our model predicts an
increase in cell size variability with growth rate, consistent with previous
experimental reports. We perturb the model to test the effect of increased
replication fork (RF) stalling frequency, or uncoupling RF stalling from the
cell-division machinery. Indeed, despite ignoring DNA and protein segregation
asymmetry, the model can faithfully reproduce quantitative changes in cell size
distributions. In our model, multi-fork replication produces multiplicative
'noise' and provides a mechanism linking growth rate and cell size variability.
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