Stopar, A, Coral, L, Di Giacomo, S et al. (2 more authors) (2018) Binary control of enzymatic cleavage of DNA origami by structural antideterminants. Nucleic Acids Research, 46 (2). pp. 995-1006. ISSN 0305-1048
Abstract
Controlling DNA nanostructure interaction with protein is essential in developing nanodevices with programmable function, reactivity, and stability for biological and medical applications. Here, we show that the sequence-specific action of restriction endonucleases towards sharp triangular or rectangular DNA origami exhibits a novel, binary 'on/off' behaviour, as canonical recognition sites are either essentially fully reactive, or strongly resistant to enzymatic cutting. Moreover, introduction of structural defects in the sharp triangle can activate an otherwise unreactive site, with a site-to-defect distance of ∼50 nm. We argue that site reactivity is dependent upon programmable, mechanical coupling in the two-dimensional DNA origami, with specific structural elements, including DNA nicks and branches proximal to the sites that can function as negative(anti) determinants of reactivity. Empirically modelling the constraints to DNA degrees of freedom associated with each recognition site in the sharp triangle can rationalize the pattern of suppressed reactivity towards nine restriction endonucleases, in substantial agreement with the experimental results. These results provide a basis for a predictive understanding of structure-reactivity correlates of specific DNA nanostructures, which will allow a better understanding of the behaviour of nucleic acids under nanoscale confinement, as well as in the rational design of functional nanodevices based on self-assembling nucleic acids.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 31 Jan 2018 12:47 |
Last Modified: | 12 Aug 2020 16:05 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/nar/gkx1204 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:126798 |