Backer, AS;
Biebricher, AS;
King, GA;
Wuite, GJL;
Heller, I;
Peterman, EJG;
(2019)
Single-molecule polarization microscopy of DNA intercalators sheds light on the structure of S-DNA.
Science Advances
, 5
(3)
, Article eaav1083. 10.1126/sciadv.aav1083.
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Abstract
DNA structural transitions facilitate genomic processes, mediate drug-DNA interactions, and inform the development of emerging DNA-based biotechnology such as programmable materials and DNA origami. While some features of DNA conformational changes are well characterized, fundamental information such as the orientations of the DNA base pairs is unknown. Here, we use concurrent fluorescence polarization imaging and DNA manipulation experiments to probe the structure of S-DNA, an elusive, elongated conformation that can be accessed by mechanical overstretching. To this end, we directly quantify the orientations and rotational dynamics of fluorescent DNA-intercalated dyes. At extensions beyond the DNA overstretching transition, intercalators adopt a tilted (θ ~ 54°) orientation relative to the DNA axis, distinct from the nearly perpendicular orientation (θ ~ 90°) normally assumed at lower extensions. These results provide the first experimental evidence that S-DNA has substantially inclined base pairs relative to those of the standard (Watson-Crick) B-DNA conformation.
| Type: | Article |
|---|---|
| Title: | Single-molecule polarization microscopy of DNA intercalators sheds light on the structure of S-DNA |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/sciadv.aav1083 |
| Publisher version: | http://dx.doi.org/10.1126/sciadv.aav1083 |
| Language: | English |
| Additional information: | Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, FLUORESCENCE MICROSCOPY, ROTATIONAL MOBILITY, FORCE SPECTROSCOPY, TORSIONAL RIGIDITY, MELTING BUBBLES, PEELED SSDNA, ORIENTATION, DYNAMICS, DYE, MACROMOLECULES |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10107492 |
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