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Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12718-23. Epub 2006 Aug 14.

Autogenous and nonautogenous control of response in a genetic network.

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  • 1Spanish National Biotechnology Centre (CNB)-Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain.


Feedback-based control methods determine the behavior of cellular systems, an example being autogenous control, the regulation of production of a protein by itself. This control strategy was theoretically shown to be superior to an equivalent but nonautogenously regulated system when based on a repressor. Although some of its advantages were later confirmed with isolated synthetic circuits, the superiority of autogenous control in natural networks remains untested. Here, we use the SOS DNA repair system of Escherichia coli, where autogenous control is part of a single-input module, as a valid model to evaluate the functional advantages and biological implications of this mechanism. We redesign the control of its master regulator, the protein LexA, so that it becomes nonautogenously controlled. We compare both systems by combining high-resolution expression measurements with mathematical modeling. We show that the stronger stability associated with the autogenous regulation prevents false triggering of the response due to transient fluctuations in the inducing signal and that this control also reduces the system recovery time at low DNA damage. Likewise, autoregulation produces responses proportional to the damage signal level. In contrast, bacteria with LexA constitutively expressed induce maximal action even for very low damage levels. This excess in response comes at a cost, because it reduces comparatively the growth rate of these cells. Our results suggest that autogenous control evolved as a strategy to optimally respond to multiple levels of input signal minimizing the costs of the response and highlights reasons why master regulators of single-input modules are mostly autorepressed.

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