title: Force measurements reveal how small binders perturb the dissociation mechanisms of DNA duplex sequences.
abstract: The force-driven separation of double-stranded DNA is crucial to the accomplishment of cellular processes like genome transactions. Ligands binding to short DNA sequences can have a local stabilizing or destabilizing effect and thus severely affect these processes. Although the design of ligands that bind to specific sequences is a field of intense research with promising biomedical applications, so far, their effect on the force-induced strand separation has remained elusive. Here, by means of AFM-based single molecule force spectroscopy, we show the co-existence of two different mechanisms for the separation of a short DNA duplex and demonstrate how they are perturbed by small binders. With the support of Molecular Dynamics simulations, we evidence that above a critical pulling rate one of the dissociation pathways becomes dominant, with a dramatic effect on the rupture forces. Around the critical threshold, we observe a drop of the most probable rupture forces for ligand-stabilized duplexes. Our results offer a deep understanding of how a stable DNA-ligand complex behaves under force-driven strand separation.
authors.affiliation: University of Liege, Department of Chemistry, Sart-Tilman B6, 4000 Liege, Belgium. fremacle@ulg.ac.be asduwez@ulg.ac.be.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Burmistrova
authors.affiliation: University of Liege, Department of Chemistry, Sart-Tilman B6, 4000 Liege, Belgium. fremacle@ulg.ac.be asduwez@ulg.ac.be.
authors.forename: Barbara
authors.initials: B
authors.lastname: Fresch
authors.affiliation: University of Liege, Department of Chemistry, Sart-Tilman B6, 4000 Liege, Belgium. fremacle@ulg.ac.be asduwez@ulg.ac.be.
authors.forename: Damien
authors.initials: D
authors.lastname: Sluysmans
authors.affiliation: University of Liege, Department of Chemistry, Sart-Tilman B6, 4000 Liege, Belgium. fremacle@ulg.ac.be asduwez@ulg.ac.be.
authors.forename: Edwin
authors.initials: E
authors.lastname: De Pauw
authors.affiliation: University of Liege, Department of Chemistry, Sart-Tilman B6, 4000 Liege, Belgium. fremacle@ulg.ac.be asduwez@ulg.ac.be.
authors.forename: Françoise
authors.initials: F
authors.lastname: Remacle
authors.affiliation: University of Liege, Department of Chemistry, Sart-Tilman B6, 4000 Liege, Belgium. fremacle@ulg.ac.be asduwez@ulg.ac.be.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Duwez
mesh_terms: D004247:DNA / Q000737:chemistry*; D008024:Ligands; D055595:Mechanical Phenomena; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation
chemical_list: D008024:Ligands; D004247:DNA