Sequence Heterogeneity Accelerates Protein Search for Targets on DNA

TL;DR

This study provides a theoretical analysis showing that DNA sequence heterogeneity can accelerate protein search for target sites, challenging previous assumptions and highlighting the influence of chemical composition and sequence symmetry.

Contribution

The paper introduces a comprehensive analytical model demonstrating that DNA heterogeneity enhances protein search efficiency, revealing new insights into genome regulation mechanisms.

Findings

Protein search is faster on heterogeneous DNA sequences.

Chemical composition near the target influences search dynamics.

Sequence heterogeneity can be a regulatory factor in biological processes.

Abstract

The process of protein search for specific binding sites on DNA is fundamentally important since it marks the beginning of all major biological processes. We present a theoretical investigation that probes the role of DNA sequence symmetry, heterogeneity and chemical composition in the protein search dynamics. Using a discrete-state stochastic approach with a first-passage events analysis, which takes into account the most relevant physical-chemical processes, a full analytical description of the search dynamics is obtained. It is found that, contrary to existing views, the protein search is generally faster on DNA with more heterogeneous sequences. In addition, the search dynamics might be affected by the chemical composition near the target site. The physical origins of these phenomena are discussed. Our results suggest that biological processes might be effectively regulated by modifying chemical composition, symmetry and heterogeneity of a genome.