Classes of fast and specific search mechanisms for proteins on DNA

TL;DR

This review discusses various search mechanisms for proteins on DNA, introduces a barrier discrimination model applicable to all transcription factor classes, and highlights its ability to enable fast, specific, and stable target recognition.

Contribution

The paper proposes a new barrier discrimination mechanism for protein-DNA search, unifying different classes of transcription factors and explaining their rapid and specific binding behavior.

Findings

Barrier discrimination mechanism applies to all transcription factor classes.

Mechanism enables fast and specific target search.

Transient features allow stable binding despite rapid unbinding.

Abstract

Problems of search and recognition appear over different scales in biological systems. In this review we focus on the challenges posed by interactions between proteins, in particular transcription factors, and DNA and possible mechanisms which allow for a fast and selective target location. Initially we argue that DNA-binding proteins can be classified, broadly, into three distinct classes which we illustrate using experimental data. Each class calls for a different search process and we discuss the possible application of different search mechanisms proposed over the years to each class. The main thrust of this review is a new mechanism which is based on barrier discrimination. We introduce the model and analyze in detail its consequences. It is shown that this mechanism applies to all classes of transcription factors and can lead to a fast and specific search. Moreover, it is shown that the mechanism has interesting transient features which allow for stability at the target despite rapid binding and unbinding of the transcription factor from the target.