Schonhoft, J.D. & Strivers, J.T. Nat. Chem. Biol. 8, 205–210 (2012).

DNA-binding proteins find their individual target sites in a process known as facilitated transport, during which the dimensionality of the search space on the DNA is reduced. The mechanism involves either one-dimensional sliding along the DNA molecule or three-dimensional hopping on and off the DNA. To separately study these events with a DNA-repair enzyme, Schonhoft & Strivers used a molecular clock, a small molecule that acts as a weak active-site inhibitor of the enzyme with a known time constant and only traps enzymes that come off the DNA, leaving the sliding ones unperturbed. Using this tool, the researchers found that the enzyme was sliding over distances of fewer than 10 base pairs, whereas they saw short and fast hops for sites at a distance of 10 or more base pairs from the original binding site. This combination of slower sliding and fast hopping ensures that the enzyme rapidly surveys the DNA and locates any site of damage.