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Phys Rev Lett. 2017 Oct 6;119(14):147801. doi: 10.1103/PhysRevLett.119.147801. Epub 2017 Oct 3.

Supercoiling DNA Locates Mismatches.

Author information

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

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.

PMID:
29053317
PMCID:
PMC5661871
DOI:
10.1103/PhysRevLett.119.147801
[Indexed for MEDLINE]
Free PMC Article

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