Small delay, big waves: a minimal delayed negative feedback model captures Escherichia coli single cell SOS kinetics

Area of Science:

• Molecular Biology
• Systems Biology
• Genetics

Background:

• Organisms must coordinate responses to environmental changes, especially when facing conflicting physiological priorities.
• Recent single-cell studies have elucidated the kinetics of the bacterial SOS response.
• Understanding regulatory control of DNA repair systems is crucial for bacterial survival.

Purpose of the Study:

• To construct a mathematical model for the regulatory control of mutagenic elements in the Escherichia coli DNA repair system.
• To investigate the role of delayed negative feedback in coordinating cellular responses to DNA damage.

Main Methods:

• Developed a mathematical model using a first-order delay differential equation for mutagenic gene repair activation and a first-order ordinary differential equation for DNA damage levels.
• Adjusted model parameters to qualitatively reproduce UV dose-dependent RecA expression.
• Incorporated parameter noise to simulate experimental fluctuations and achieved quantitative agreement for response peak timing.

Main Results:

• The model qualitatively reproduces UV dose-dependent RecA expression, including peak occurrence, amplitude, and timing.
• Parameter noise in the model captures observed fluctuations in experimental data.
• Quantitative agreement was achieved for the timing of response peaks across different UV doses.

Conclusions:

• Delayed negative feedback is a key regulatory mechanism for mutagenic gene repair in Escherichia coli.
• The developed model demonstrates how delayed regulatory mechanisms control critical organismic responses with potential negative side effects.
• This study provides insights into the complex coordination of cellular responses to DNA damage.