Roles of Cro2 and CI2 binding to OR operators in controlling lysogeny stability during prophage induction
Pang, Y.; Lei, X.; Manuchehrfar, F.; Du, L.; Liang, J.
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The lysogeny-lysis switch in bacteriophage lambda serves as a model for understanding cell fate decisions. The molecular network controlling this switch has been explored through extensive experimental and computational studies. Yet, the specific role of protein-DNA interactions, like the binding of CI2 and Cro2 proteins to operator sites, in regulating lysogeny stability during prophage induction remains less under-stood. This study employs a minimalistic model and the Accurate Chemical Master Equation (ACME) method to construct detailed probability landscapes of the networks behavior under varying conditions, such as different dissociation and CI2 degradation rates which simulate UV irradiation effects. Our findings indicate that Cro2 binding at OR3 and CI2 at OR1 significantly influence lysogeny stability, with the former destabilizing and the latter stabilizing it. Conversely, interactions at OR1 by Cro2 and OR3 by CI show minimal impact on this stability. Through the ACME approach, we could examine the networks global behavior under conditions unapproachable by conventional stochastic simulations. This study highlights the critical roles of specific protein-DNA interactions in maintaining lysogeny and provides insight into the broader dynamics of the lysogeny-lysis switch under various physiological stresses.
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