Preprints from the Kleckner Lab
1. A general quantitative relation linking bacterial cell growth and the cell cycle
Hai Zheng, Yang Bai, Meiling Jiang, Taku A. Tokuyasu, Xiongliang Huang, Fajun Zhong, Xiongfei Fu, Nancy Kleckner, Terence Hwa, Chenli Liu.
doi: https://doi.org/10.1101/795013
Abstract
The foundation of bacterial cell cycle studies has long resided in two interconnected dogmas between biomass growth, DNA replication, and cell division during exponential growth: the SMK growth law that relates cell mass (a measure of cell size) to growth rate, and Donachie’s hypothesis of a growth-rate-independent initiation mass. These dogmas have spurred many efforts to understand their molecular bases and physiological consequences. Most of these studies focused on fast-growing cells, with doubling times shorter than 60 min. Here, we systematically studied the cell cycle of E. coli for a broad range of doubling times (24 min to over 10 hr), with particular attention on steady-state growth. Surprisingly, we observed that neither dogma held across the range of growth rates examined. In their stead, a new linear relation unifying the slow- and fast-growth regimes was revealed between the cell mass and the number of cell divisions it takes to replicate and segregate a newly initiated pair of replication origins. This and other findings in this study suggest a single-cell division model, which not only reproduces the bulk relations observed but also recapitulates the adder phenomenon established recently for stochastically dividing cells. These results allowed us to develop quantitative insight into the bacterial cell cycle, providing a firm new foundation for the study of bacterial growth physiology.
2. DNA Double Strand Break Repair in E. coli Perturbs Cell Division and Chromosome Dynamics
M.A. White, E. Darmon, M.A. Lopez-Vernaza, D.R.F. Leach
doi: https://doi.org/10.1101/802389
Abstract
To prevent the transmission of damaged genomic material between generations, cells require a system for accommodating DNA repair within their cell cycles. We have previously shown that Escherichia coli cells subject to a single, repairable site-specific DNA double-strand break (DSB) per DNA replication cycle reach a new average cell length, with a negligible effect on population growth rate. We show here that this new cell size distribution is caused by a DSB repair-dependent delay in completion of cell division. This delay occurs despite unperturbed cell size regulated initiation of both chromosomal DNA replication and cell division. Furthermore, despite DSB repair altering the profile of DNA replication across the genome, the time required to complete chromosomal duplication is invariant. The delay in completion of cell division is accompanied by a DSB repair-dependent delay in individualization of sister nucleoids. We suggest that DSB repair events create inter-sister connections that persist until those chromosomes are separated by a closing septum.
