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Direct Measurement of Interhelical DNA Repulsion and Attraction by Quantitative Cross-Linking
[Image: see text] To better understand the forces that mediate nucleic acid compaction in biology, we developed the disulfide cross-linking approach xHEED (X-linking of Helices to measure Electrostatic Effects at Distance) to measure the distance-dependent encounter frequency of two DNA helices in s...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8815069/ https://www.ncbi.nlm.nih.gov/pubmed/35073489 http://dx.doi.org/10.1021/jacs.1c11122 |
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author | Hamilton, Ian Gebala, Magdalena Herschlag, Daniel Russell, Rick |
author_facet | Hamilton, Ian Gebala, Magdalena Herschlag, Daniel Russell, Rick |
author_sort | Hamilton, Ian |
collection | PubMed |
description | [Image: see text] To better understand the forces that mediate nucleic acid compaction in biology, we developed the disulfide cross-linking approach xHEED (X-linking of Helices to measure Electrostatic Effects at Distance) to measure the distance-dependent encounter frequency of two DNA helices in solution. Using xHEED, we determined the distance that the electrostatic potential extends from DNA helices, the dependence of this distance on ionic conditions, and the magnitude of repulsion when two helices approach one another. Across all conditions tested, the potential falls to that of the bulk solution within 15 Å of the major groove surface. For separations of ∼30 Å, we measured a repulsion of 1.8 kcal/mol in low monovalent ion concentration (30 mM Na(+)), with higher Na(+) concentrations ameliorating this repulsion, and 2 M Na(+) or 100 mM Mg(2+) eliminating it. Strikingly, we found full screening at very low Co(3+) concentrations and net attraction at higher concentrations, without the higher-order DNA condensation that typically complicates studies of helical attraction. Our measurements define the relevant distances for electrostatic interactions of nucleic-acid helices in biology and introduce a new method to propel further understanding of how these forces impact biological processes. |
format | Online Article Text |
id | pubmed-8815069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-88150692022-02-07 Direct Measurement of Interhelical DNA Repulsion and Attraction by Quantitative Cross-Linking Hamilton, Ian Gebala, Magdalena Herschlag, Daniel Russell, Rick J Am Chem Soc [Image: see text] To better understand the forces that mediate nucleic acid compaction in biology, we developed the disulfide cross-linking approach xHEED (X-linking of Helices to measure Electrostatic Effects at Distance) to measure the distance-dependent encounter frequency of two DNA helices in solution. Using xHEED, we determined the distance that the electrostatic potential extends from DNA helices, the dependence of this distance on ionic conditions, and the magnitude of repulsion when two helices approach one another. Across all conditions tested, the potential falls to that of the bulk solution within 15 Å of the major groove surface. For separations of ∼30 Å, we measured a repulsion of 1.8 kcal/mol in low monovalent ion concentration (30 mM Na(+)), with higher Na(+) concentrations ameliorating this repulsion, and 2 M Na(+) or 100 mM Mg(2+) eliminating it. Strikingly, we found full screening at very low Co(3+) concentrations and net attraction at higher concentrations, without the higher-order DNA condensation that typically complicates studies of helical attraction. Our measurements define the relevant distances for electrostatic interactions of nucleic-acid helices in biology and introduce a new method to propel further understanding of how these forces impact biological processes. American Chemical Society 2022-01-24 2022-02-02 /pmc/articles/PMC8815069/ /pubmed/35073489 http://dx.doi.org/10.1021/jacs.1c11122 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Hamilton, Ian Gebala, Magdalena Herschlag, Daniel Russell, Rick Direct Measurement of Interhelical DNA Repulsion and Attraction by Quantitative Cross-Linking |
title | Direct Measurement of Interhelical DNA Repulsion and
Attraction by Quantitative Cross-Linking |
title_full | Direct Measurement of Interhelical DNA Repulsion and
Attraction by Quantitative Cross-Linking |
title_fullStr | Direct Measurement of Interhelical DNA Repulsion and
Attraction by Quantitative Cross-Linking |
title_full_unstemmed | Direct Measurement of Interhelical DNA Repulsion and
Attraction by Quantitative Cross-Linking |
title_short | Direct Measurement of Interhelical DNA Repulsion and
Attraction by Quantitative Cross-Linking |
title_sort | direct measurement of interhelical dna repulsion and
attraction by quantitative cross-linking |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8815069/ https://www.ncbi.nlm.nih.gov/pubmed/35073489 http://dx.doi.org/10.1021/jacs.1c11122 |
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