RecA structure kinetics determine SOS dynamics and predict spontaneous cell death
- 1University of Oxford
Abstract
Even under optimal growth conditions, bacterial cells experience endogenous stresses that threaten cellular function. Individual cells sporadically activate stress responses to restore homeostasis, but some cells ultimately die. The SOS response to DNA damage is particularly heterogeneous, but the origin of its spontaneous activation and its relationship to cell fate remain unclear. Here, we imaged fluorescently labelled RecA in single Escherichia coli cells under steady-state unperturbed growth using microfluidics. We find that RecA* structures assemble frequently near replication forks and precede SOS response pulses. RecA* structure lifetime quantitatively encodes the magnitude of SOS induction: longer-lived structures promote greater LexA degradation and larger SOS pulses. Thus, cell-to-cell variability in spontaneous SOS activation reflects differences in the repair kinetics of endogenous DNA damage events. By tracking cell lineages over time, we further show that RecA* structures are strong and early predictors of cell fate. Elevated RecA* structure presence emerges up to six generations before spontaneous cell death in over 75% of cases, before other physiological disturbances become detectable. Together, our results establish spontaneous SOS activation as a quantitative readout of endogenous DNA damage processing and identify failure to resolve such damage as a major route to spontaneous bacterial cell death.
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BibTeX
@misc{pollacco2026reca,
title = {{RecA structure kinetics determine SOS dynamics and predict spontaneous cell death}},
author = {J. J. Pollacco and T. Haygarth and A. Couturier and C. Lesterlin and D. J. Sherratt and R. E. Baker and P. K. Maini and S. Uphoff},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.760072},
url = {https://www.biorxiv.org/content/10.64898/2026.10.19.760072v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - RecA structure kinetics determine SOS dynamics and predict spontaneous cell death
AU - J. J. Pollacco
AU - T. Haygarth
AU - A. Couturier
AU - C. Lesterlin
AU - D. J. Sherratt
AU - R. E. Baker
AU - P. K. Maini
AU - S. Uphoff
PY - 2026
DA - 2026/10/19
PB - bioRxiv
DO - 10.64898/2026.10.19.760072
UR - https://www.biorxiv.org/content/10.64898/2026.10.19.760072v1
AB - Even under optimal growth conditions, bacterial cells experience endogenous stresses that threaten cellular function. Individual cells sporadically activate stress responses to restore homeostasis, but some cells ultimately die. The SOS response to DNA damage is particularly heterogeneous, but the origin of its spontaneous activation and its relationship to cell fate remain unclear. Here, we imaged fluorescently labelled RecA in single Escherichia coli cells under steady-state unperturbed growth using microfluidics. We find that RecA* structures assemble frequently near replication forks and precede SOS response pulses. RecA* structure lifetime quantitatively encodes the magnitude of SOS induction: longer-lived structures promote greater LexA degradation and larger SOS pulses. Thus, cell-to-cell variability in spontaneous SOS activation reflects differences in the repair kinetics of endogenous DNA damage events. By tracking cell lineages over time, we further show that RecA* structures are strong and early predictors of cell fate. Elevated RecA* structure presence emerges up to six generations before spontaneous cell death in over 75% of cases, before other physiological disturbances become detectable. Together, our results establish spontaneous SOS activation as a quantitative readout of endogenous DNA damage processing and identify failure to resolve such damage as a major route to spontaneous bacterial cell death.
ER -