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

TL;DR

This paper investigates how proteins efficiently locate specific DNA sites by analyzing the role of intersegment transfer, which enhances search speed beyond simple diffusion models, especially when proteins are mostly DNA-bound.

Contribution

It provides a quantitative analysis of intersegment transfer's impact on DNA target search rates in dense DNA environments, integrating DNA motion and protein sliding.

Findings

Intersegment transfer significantly accelerates target search.

Proteins spend most of their time adsorbed on DNA during search.

The model explains observed rapid search rates in vivo.

Abstract

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.