  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.
