Supercoiling DNA locates mismatches

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.

References in corpus (2)

• Plectoneme tip bubbles: Coupled denaturation and writhing in supercoiled DNA
• Mechanical response of plectonemic DNA: an analytical solution

Cited by in corpus (5)

• Physical Principles of Retroviral Integration in the Human Genome
• Coarse-grained modelling of strong DNA bending II: Cyclization
• Base-pair mismatch can destabilize small DNA loops through cooperative kinking
• Two-Phase Dynamics of DNA Supercoiling based on DNA Polymer Physics
• Phase Diagram and Snap-Off Transition for a Twisted Party Balloon