Modulation of DNA loop lifetimes by the free energy of loop formation

TL;DR

This study investigates how the free energy of DNA loop formation influences the lifetimes of DNA loops, revealing that loop dynamics depend on DNA elasticity and protein interactions, with implications for gene regulation.

Contribution

It introduces a model linking DNA loop lifetimes to deformation free energy and protein-DNA interaction length, advancing understanding of DNA looping dynamics.

Findings

Loop association and dissociation depend on DNA elasticity.

Looping and unlooping rates scale with the J factor.

Finite protein-DNA interaction length influences dissociation dynamics.

Abstract

Storage and retrieval of the genetic information in cells is a dynamic process that requires the DNA to undergo dramatic structural rearrangements. DNA looping is a prominent example of such a structural rearrangement that is essential for transcriptional regulation in both prokaryotes and eukaryotes, and the speed of such regulations affects the fitness of individuals. Here, we examine the in vitro looping dynamics of the classic Lac repressor gene-regulatory motif. We show that both loop association and loop dissociation at the DNA-repressor junctions depend on the elastic deformation of the DNA and protein, and that both looping and unlooping rates approximately scale with the looping J factor, which reflects the system's deformation free energy. We explain this observation by transition state theory and model the DNA-protein complex as an effective worm-like chain with twist. We introduce a finite protein-DNA binding interaction length, in competition with the characteristic DNA deformation length scale, as the physical origin of the previously unidentified loop dissociation dynamics observed here, and discuss the robustness of this behavior to perturbations in several polymer parameters.