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Protein complexes involved in DNA mismatch repair appear to diffuse alongdsDNA in order to locate a hemimethylated incision site via a dissociativemechanism. Here, we study the probability that these complexes locate a giventarget site via a semi-analytic, Monte Carlo calculation that tracks theassociation and dissociation of the complexes. We compare such probabilities tothose obtained using a non-dissociative diffusive scan, and determine that forexperimentally observed diffusion constants, search distances, and searchdurations $\textit{in vitro}$, there is neither a significant advantage nordisadvantage associated with the dissociative mechanism in terms of probabilityof successful search, and that both search mechanisms are highly efficient fora majority of hemimethylated site distances. Furthermore, we examine the spaceof physically realistic diffusion constants, hemimethylated site distances, andassociation lifetimes and determine the regions in which dissociative searchingis more or less efficient than non-dissociative searching. We conclude that thedissociative search mechanism is advantageous in the majority of the physicallyrealistic parameter space.

Potential evolutionary advantage of a dissociative search mechanism in DNA mismatch repair