Pyne, Alice L B, Noy, Agnes orcid.org/0000-0003-0673-8949, Main, Kavit H S et al. (10 more authors) (2021) Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and major groove recognition by triplex-forming oligonucleotides. Nature Communications. 1053. ISSN 2041-1723
Abstract
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, that may have broader implications for DNA interactions with other molecular species.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2021 |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Physics (York) |
Funding Information: | Funder Grant number EPSRC EP/N027639/1 |
Depositing User: | Pure (York) |
Date Deposited: | 19 Feb 2021 10:00 |
Last Modified: | 22 Jan 2025 00:16 |
Published Version: | https://doi.org/10.1038/s41467-021-21243-y |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-021-21243-y |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:171355 |