Fig. 1.

Protein search pathways and experimental approach. (A) Facilitated diffusion model with sliding and hopping resulting in probing of already visited sites (oversampling) on straight DNA. (B) On coiled DNA the enzyme can be captured by a segment it has not yet visited, leading to an intersegmental jump and reduction of oversampling. Because of random polymer fluctuations a protein performing an intersegmental jump at instant 1 will, upon unbinding at instant 1′ have moved far away from the original segment, accelerating the search process. (C) Experimental approach. Single DNA molecules are held between two beads in optical tweezers. EcoRV cleavage rates are measured at different DNA extensions. The conformational freedom of the DNA at these extensions can be divided into three regimes: (entropically) stretched DNA (Top), globular DNA (relaxed coil) (Middle), and a DNA coil that is squeezed between the beads. (Bottom)