Twist, Stretch and Melt: Quantifying How DNA Complies to Tension

Abstract

Central biological processes involve continuous mechanical manipulation of DNA. In cells, DNA is constantly twisted, bended and stretched by numerous proteins mediating genome compaction, gene regulation, expression, and DNA repair. Consequently, to understand these processes, it is imperative to have an in-depth understanding of how DNA complies to mechanical stress. The helical structure and the sequence of DNA, two physical features that have a strong impact on protein-DNA interactions, are not incorporated in the current quantitative descriptions of DNA elasticity. Here we connect well-defined force-extension measurements with a novel structure-guided model for DNA elasticity, the twistable worm like chain model. This analytical description incorporates the essential physical characteristics of DNA, including how its helicity depends on extension. In addition, at forces exceeding ∼65 pN, when DNA overstretches and melts, our experimental assay exposes rich features that can be fully attributed to the underlying base sequence. An equilibrium thermodynamic model is presented that quantitatively captures this melting behaviour solely based on the knowledge of DNA sequence and elasticity. These results offer a new standard description for the mechanics of DNA and enable deeper quantitative insight into the physical interactions of DNA-associated proteins.