Stretching chimeric DNA: a test for the putative S-form

TL;DR

This study models how sequence heterogeneity affects DNA overstretching, proposing a test to distinguish between force-induced denaturation and S-DNA formation by observing spatially segregated transitions.

Contribution

It introduces a statistical mechanical model showing how chimeric DNA sequences exhibit distinct overstretching transitions, providing a potential experimental test for the existence of S-DNA.

Findings

Chimeric sequences show two distinct overstretching plateaux.

Force difference between plateaux depends on pulling rate.

Spatially segregated transitions suggest different conformational states.

Abstract

Double-stranded DNA `overstretches' at a pulling force of about 65 pN, increasing in length by a factor of 1.7. The nature of the overstretched state is unknown, despite its considerable importance for DNA's biological function and technological application. Overstretching is thought by some to be a force-induced denaturation, and by others to consist of a transition to an elongated, hybridized state called S-DNA. Within a statistical mechanical model we consider the effect upon overstretching of extreme sequence heterogeneity. `Chimeric' sequences possessing halves of markedly different AT composition elongate under fixed external conditions via distinct, spatially segregated transitions. The corresponding force-extension data display two plateaux at forces whose difference varies with pulling rate in a manner that depends qualitatively upon whether the hybridized S-form is accessible. This observation implies a test for S-DNA that could be performed in experiment. Our results suggest that qualitatively different, spatially segregated conformational transitions can occur at a single thermodynamic state within single molecules of DNA.