RT Journal Article
SR Electronic
T1 Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and recognition
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 863423
DO 10.1101/863423
A1 Alice L. B. Pyne
A1 Agnes Noy
A1 Kavit Main
A1 Victor Velasco-Berrelleza
A1 Michael M. Piperakis
A1 Lesley A. Mitchenall
A1 Fiorella M. Cugliandolo
A1 Joseph G. Beton
A1 Clare E.M. Stevenson
A1 Bart W. Hoogenboom
A1 Andrew D. Bates
A1 Anthony Maxwell
A1 Sarah A. Harris
YR 2020
UL http://biorxiv.org/content/early/2020/05/04/863423.abstract
AB In the cell, DNA is arranged into highly-organised and topologically-constrained (supercoiled) structures. It remains unclear how this supercoiling affects the detailed double-helical structure of DNA, largely because of limitations in spatial resolution of the available biophysical tools. Here, we overcome these limitations, by a combination of atomic force microscopy (AFM) and atomistic molecular dynamics (MD) simulations, to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution. We observe that negative superhelical stress induces local variation in the canonical B-form DNA structure by introducing kinks and defects that affect global minicircle structure and flexibility. We probe how these local and global conformational changes affect DNA interactions through the binding of triplex-forming oligonucleotides to DNA minicircles. We show that the energetics of triplex formation is governed by a delicate balance between electrostatics and bonding interactions. Our results provide mechanistic insight into how DNA supercoiling can affect molecular recognition.Competing Interest StatementThe authors have declared no competing interest.