The “monkey-bar” mechanism for searching for the DNA target site: The molecular determinants

DNA recognition by DNA-binding proteins, which is a pivotal event in most gene regulatory processes, is often preceded by an extensive search for the correct site. A facilitated diffusion process, in which a DBP combines 3D diffusion in solution with 1D sliding along DNA, has been suggested to explain how proteins can locate their target sites on DNA much faster than predicted by 3D diffusion alone. One of the key mechanisms in the localization of the target by a DNA-binding protein is intersegment transfer in which the protein forms a bridged intermediate between two distant DNA regions. This jumping mechanism is more enhanced when the DNA-binding protein is asymmetric in its structure or its dynamics. We suggest that asymmetry supports the “monkey bar” mechanism, in which different domains of the protein interact with different DNA regions. In this minireview, we discuss how the molecular architectures of the proteins and DNA may modulate the efficiency of monkey bar dynamics.