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

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.

References in corpus (5)

• Probing the elastic limit of DNA bending
• Kinetics of Interior Loop Formation in Semiflexible Chains
• Diffusion-limited loop formation of semiflexible polymers: Kramers theory and the intertwined time scales of chain relaxation and closing
• Sequence Dependence of Transcription Factor-Mediated DNA Looping
• Poly(dA:dT)-rich DNAs are highly flexible in the context of DNA looping

Cited by in corpus (7)

• Coarse-grained modelling of strong DNA bending II: Cyclization
• First hitting times to intermittent targets
• Twist-bend coupling, twist waves and the shape of DNA loops
• Base-pair mismatch can destabilize small DNA loops through cooperative kinking
• Phase diagram of the ground states of DNA condensates
• Facilitation of DNA loop formation by protein-DNA non-specific interactions
• Optimizing the random search of a finite-lived target by a Lévy flight