How a protein searches for its specific site on DNA: The role of intersegment transfer

Proteins are known to locate their specific targets on DNA up to two orders of magnitude faster than predicted by the Smoluchowski three-dimensional diffusion rate. One of the mechanisms proposed to resolve this discrepancy is termed intersegment transfer. Many proteins have two DNA binding sites and can transfer from one DNA segment to another without dissociation to water. We calculate the target search rate for such proteins in a dense globular DNA, taking into account intersegment transfer working in conjunction with DNA motion and protein sliding along DNA. We show that intersegment transfer plays a very important role in cases where the protein spends most of its time adsorbed on DNA.