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Supercoiling DNA locates mismatches

Andrew Dittmore, Sumitabha Brahmachari, Yasuhara Takagi, John F. Marko, Keir C. Neuman
doi: https://doi.org/10.1101/130567
Andrew Dittmore
1Laboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
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Sumitabha Brahmachari
2Department of Physics and Astronomy, Northwestern University, Evanston IL 60208
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Yasuhara Takagi
1Laboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
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John F. Marko
2Department of Physics and Astronomy, Northwestern University, Evanston IL 60208
3Department of Molecular Biosciences, Northwestern University, Evanston IL 60208
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Keir C. Neuman
1Laboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
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Abstract

We present a method of detecting sequence defects by supercoiling DNA with magnetic tweezers. The method is sensitive to a single mismatched base pair in a DNA sequence of several thousand base pairs. We systematically compare DNA molecules with 0 to 16 adjacent mismatches at 1 M monovalent salt and 3.5 pN force and show that, under these conditions, a single plectoneme forms and is stably pinned at the defect. We use these measurements to estimate the energy and degree of end-loop kinking at defects. From this, we calculate the relative probability of plectoneme pinning at the mismatch under physiologically relevant conditions. Based on this estimate, we propose that DNA supercoiling could contribute to mismatch and damage sensing in vivo.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 25, 2017.
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Supercoiling DNA locates mismatches
Andrew Dittmore, Sumitabha Brahmachari, Yasuhara Takagi, John F. Marko, Keir C. Neuman
bioRxiv 130567; doi: https://doi.org/10.1101/130567
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Supercoiling DNA locates mismatches
Andrew Dittmore, Sumitabha Brahmachari, Yasuhara Takagi, John F. Marko, Keir C. Neuman
bioRxiv 130567; doi: https://doi.org/10.1101/130567

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