# Supercoiling DNA locates mismatches

## TL;DR

This paper introduces a magnetic tweezers-based method to detect single mismatched base pairs in DNA by observing supercoiling-induced plectoneme pinning, which could aid in DNA damage sensing.

## Contribution

The study demonstrates that supercoiling can locate mismatches in DNA and provides a quantitative framework for understanding plectoneme pinning at defects.

## Key findings

- Single mismatches cause stable plectoneme pinning.
- Plectoneme formation is sensitive to mismatch number and conditions.
- Supercoiling may play a role in DNA damage detection in vivo.

## 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.