title: 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.
authors.affiliation: Departments of Physics.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Biochemistry and Molecular Biophysics, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158; and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Peter
authors.initials: P
authors.lastname: Mulligan
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Spakowitz
authors.affiliation: Applied Physics, and Biology, California Institute of Technology, Pasadena, CA 91125; phillips@pboc.caltech.edu.
authors.forename: Rob
authors.initials: R
authors.lastname: Phillips
mesh_terms: D001703:Biophysics; D004247:DNA / Q000737:chemistry*; D004548:Elasticity; D005786:Gene Expression Regulation; D007700:Kinetics; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011108:Polymers / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D011108:Polymers; D011506:Proteins; D004247:DNA
keywords: loop-modulated kinetic rates; protein-mediated DNA looping; transition state