Shepherd, Jack, Greenall, Robert James orcid.org/0000-0002-0922-1243, Probert, Matt orcid.org/0000-0002-1130-9316 et al. (2 more authors) (2020) The emergence of sequence-dependent structural motifs in stretched, torsionally 2 constrained DNA. Nucleic Acids Research. gkz1227. 1748–1763. ISSN 0305-1048
Abstract
The double-helical structure of DNA results from canonical base pairing and stacking interactions. However, variations from steady-state conformations resulting from mechanical perturbations in cells have physiological relevance but their dependence on sequence remains unclear. Here, we use molecular dynamics simulations showing sequence differences result in markedly different structural motifs upon physiological twisting and stretching. We simulate overextension on different sequences of DNA ((AA)12, (AT)12, (CC)12 and (CG)12) with supercoiling densities at 200 and 50 mM salt concentrations. We find that DNA denatures in the majority of stretching simulations, surprisingly including those with over-twisted DNA. GC-rich sequences are observed to be more stable than AT-rich ones, with the specific response dependent on the base pair order. Furthermore, we find that (AT)12 forms stable periodic structures with non-canonical hydrogen bonds in some regions and non-canonical stacking in others, whereas (CG)12 forms a stacking motif of four base pairs independent of supercoiling density. Our results demonstrate that 20–30% DNA extension is sufficient for breaking B-DNA around and significantly above cellular supercoiling, and that the DNA sequence is crucial for understanding structural changes under mechanical stress. Our findings have important implications for the activities of protein machinery interacting with DNA in all cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2020. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Physics (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Funding Information: | Funder Grant number EPSRC EP/N027639/1 |
Depositing User: | Pure (York) |
Date Deposited: | 23 Dec 2019 15:10 |
Last Modified: | 22 Jan 2025 00:13 |
Published Version: | https://doi.org/10.1093/nar/gkz1227 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1093/nar/gkz1227 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:154928 |