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Supercoiling DNA Locates Mismatches

Andrew Dittmore, Sumitabha Brahmachari, Yasuharu Takagi, John F. Marko, and Keir C. Neuman
Phys. Rev. Lett. 119, 147801 – Published 3 October 2017
Physics logo See Synopsis: Twisting DNA Locates its Defects
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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 3.6 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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  • Received 26 April 2017

DOI:https://doi.org/10.1103/PhysRevLett.119.147801

© 2017 American Physical Society

Physics Subject Headings (PhySH)

Condensed Matter, Materials & Applied PhysicsAtomic, Molecular & OpticalInterdisciplinary PhysicsPhysics of Living SystemsPolymers & Soft Matter

Synopsis

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Twisting DNA Locates its Defects

Published 3 October 2017

Single base-pair mismatches in DNA can be pinpointed by twisting the molecule until it buckles.

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Authors & Affiliations

Andrew Dittmore1, Sumitabha Brahmachari2, Yasuharu Takagi1, John F. Marko2,3, and Keir C. Neuman1

  • 1Laboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
  • 2Department of Physics and Astronomy, Northwestern University, Evanston, Illinois 60208, USA
  • 3Department of Molecular Biosciences, Northwestern University, Evanston Illinois 60208, USA

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Issue

Vol. 119, Iss. 14 — 6 October 2017

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