PT  - JOURNAL ARTICLE
AU  - Dittmore, Andrew
AU  - Brahmachari, Sumitabha
AU  - Takagi, Yasuhara
AU  - Marko, John F.
AU  - Neuman, Keir C.
TI  - Supercoiling DNA locates mismatches
AID  - 10.1101/130567
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 130567
4099  - http://biorxiv.org/content/early/2017/04/25/130567.short
4100  - http://biorxiv.org/content/early/2017/04/25/130567.full
AB  - 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.