Stochastic ratchet mechanisms for replacement of proteins bound to DNA

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 multistep replacement of DNA-bound proteins by solution-phase proteins. For four different kinetic scenarios we calculate the dependence 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 nonspecifically to DNA can describe experiments on exchanges between the nonspecific DNA-binding proteins Fis-Fis and Fis-HU, and (3) that a binding specific model describes experiments on the exchange of CueR proteins on specific binding sites.