Sequence Heterogeneity Accelerates Protein Search for Targets on DNA

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.

10 pages, 5 figures

References in corpus (4)

• Facilitated diffusion on mobile DNA: configurational traps and sequence heterogeneity
• How does a protein search for the specific site on DNA: the role of disorder
• Protein search for multiple targets on DNA
• Nonspecific Protein-DNA Binding Is Widespread in the Yeast Genome

Cited by in corpus (4)

• Molecular search with conformational change: One-dimensional discrete-state stochastic model
• On the Mechanism of Homology Search by RecA Protein Filaments
• The Effect of Obstacles in Multi-Site Protein Target Search with DNA Looping
• Facilitation of DNA loop formation by protein-DNA non-specific interactions