RT Journal Article
SR Electronic
T1 Understanding the paradoxical mechanical response of in-phase A-tracts at different force regimes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 854968
DO 10.1101/854968
A1 Alberto Marin-Gonzalez
A1 Cesar L. Pastrana
A1 Rebeca Bocanegra
A1 Alejandro Martín-González
A1 J.G. Vilhena
A1 Rubén Pérez
A1 Borja Ibarra
A1 Clara Aicart-Ramos
A1 Fernando Moreno-Herrero
YR 2019
UL http://biorxiv.org/content/early/2019/11/26/854968.abstract
AB A-tracts are A:T rich DNA sequences that exhibit unique structural and mechanical properties associated with several functions in vivo. The crystallographic structure of A-tracts has been well characterized. However, their response to forces remains unknown and the variability of their flexibility reported for different length scales has precluded a comprehensive description of the mechanical properties of these molecules. Here, we rationalize the mechanical properties of A-tracts across multiple length scales using a combination of single-molecule experiments and theoretical polymer models applied to DNA sequences present in the C. elegans genome. Atomic Force Microscopy imaging shows that phased A-tracts induce long-range (∼200 nm) bending. Moreover, the enhanced bending originates from an intrinsically bent structure rather than as a consequence of larger flexibility. In support of this, our data were well described with a theoretical model based on the worm-like chain model that includes intrinsic bending. Magnetic tweezers experiments confirm that the observed bent is intrinsic to the sequence and does not rely on particular ionic conditions. Using optical tweezers, we assess the local rigidity of A-tracts at high forces and unravel an unusually stiff character of these sequences, as quantified by their large stretch modulus. Our work rationalizes the complex multiscale flexibility of A-tracts, shedding light on the cryptic character of these sequences.