[en] The force-driven separation of double-stranded DNA is crucial to the accomplishment of cellular pro- cesses 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 mole- cule 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 Mole- cular 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
Disciplines :
Physical, chemical, mathematical & earth Sciences: Multidisciplinary, general & others
Author, co-author :
Burmistrova, Anastasia ; Université de Liège - ULiège > Département de chimie (sciences) > Nanochimie et systèmes moléculaires
Fresch, Barbara ; Université de Liège > Département de chimie (sciences) > Laboratoire de chimie physique théorique
Sluysmans, Damien ; Université de Liège > Département de chimie (sciences) > Nanochimie et systèmes moléculaires
De Pauw, Edwin ; Université de Liège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Remacle, Françoise ; Université de Liège > Département de chimie (sciences) > Laboratoire de chimie physique théorique
Duwez, Anne-Sophie ; Université de Liège > Département de chimie (sciences) > Nanochimie et systèmes moléculaires
Language :
English
Title :
Force measurements reveal how small binders perturb the dissociation mechanisms of DNA duplex sequences
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