Protein motion from non-specific to specific DNA by three-dimensional routes aided by supercoiling

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Abstract
DNA‐binding proteins are generally thought to locate their target sites by first associating with the DNA at random and then translocating to the specific site by one‐dimensional (1D) diffusion along the DNA. We report here that non‐specific DNA conveys proteins to their target sites just as well when held near the target by catenation as when co‐linear with the target. Hence, contrary to the prevalent view, proteins move from random to specific sites primarily by three‐dimensional (3D) rather than 1D pathways, by multiple dissociation/re‐association events within a single DNA molecule. We also uncover a role for DNA supercoiling in target‐site location. Proteins find their sites more readily in supercoiled than in relaxed DNA, again indicating 3D rather than 1D routes.