ABSTRACTIn natural environments bacteria are frequently exposed to sub-lethal levels of DNA damage. Exposure to DNA damaging agents lead to the induction of the DNA damage response (called the SOS response in Escherichia coli), which helps bacteria overcome the damage. Natural environments also vary in the degree of nutrient availability, resulting in distinct physiological changes in the bacteria, including modification of the growth rate and of the amount of DNA per cell. Such change may have

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... direct implications on the susceptibility of bacteria to DNA damage and their capacity to repair their chromosomes. This raises the question of the interplay between cell physiology and DNA repair. Here, we evaluated the impact of varying the nutrient availability on the expression of the SOS response induced by chronic sub-lethal level of DNA damage in E. coli. We found the expression of the SOS regulon to be highly-heterogeneous at the single-cell level in all growth conditions. Surprisingly, we observed a larger fraction of highly induced cells in slow growth conditions as compared with fast growth conditions, despite a higher rate of SOS induction in fast growth conditions. This counter-intuitive result can be explained by the dynamic balance between the rate of SOS induction and the difference in division rates for highly SOS induced cells versus cells that exhibit moderate induction. Taken together, our data illustrates how cell division and physiology come together to produce growth-dependent heterogeneity in the DNA damage response. More generally, this work suggests that when a stress creates heterogeneity in the division times, the dynamics of the whole population will be affected.