How do DNA-bound proteins leave their binding sites? The role of facilitated dissociation

Abstract

Dissociation of a protein from DNA is often assumed to be described by an off rate that is independent of other molecules in solution. Recent experiments and computational analyses have challenged this view by showing that unbinding rates (residence times) of DNA-bound proteins can depend on concentrations of nearby molecules that are competing for binding. This ‘facilitated dissociation’ (FD) process can occur at the single-binding site level via formation of a ternary complex, and can dominate over ‘spontaneous dissociation’ at low (submicromolar) concentrations. In the crowded intracellular environment FD introduces new regulatory possibilities at the level of individual biomolecule interactions.