Stochastic Ratchet Mechanisms for Replacement of Proteins Bound to DNA

TL;DR

This paper develops a theoretical framework for understanding how proteins bound to DNA are replaced by proteins from the surrounding solution, highlighting the effects of multi-step processes and different binding scenarios on unbinding and replacement rates.

Contribution

It introduces a multi-step replacement model for DNA-bound proteins, analyzing various kinetic scenarios and their dependence on solution protein concentration.

Findings

Progressive rezipping significantly influences replacement rates.

Non-specific binding models explain Fis-HU protein exchange.

Specific binding models account for CueR protein exchange.

Abstract

Experiments indicate that unbinding rates of proteins from DNA can depend on the concentration of proteins in nearby solution. Here we present a theory of multi-step replacement of DNA-bound proteins by solution-phase proteins. For four different kinetic scenarios we calculate the depen- dence of protein unbinding and replacement rates on solution protein concentration. We find (1) strong effects of progressive 'rezipping' of the solution-phase protein onto DNA sites liberated by 'unzipping' of the originally bound protein; (2) that a model in which solution-phase proteins bind non-specifically to DNA can describe experiments on exchanges between the non specific DNA- binding proteins Fis-Fis and Fis-HU; (3) that a binding specific model describes experiments on the exchange of CueR proteins on specific binding sites.