# Base-pair mismatch can destabilize small DNA loops through cooperative kinking

## TL;DR

This study reveals that base pair mismatches in small DNA loops can destabilize their kinetic stability by promoting cooperative kinking, which transfers bending stress and affects loop lifetime.

## Contribution

It introduces a three-state model explaining how base pair mismatches influence DNA loop stability through cooperative kinking mechanisms.

## Key findings

- Mismatches decrease DNA loop lifetime despite reducing bending stress.
- Mismatches at the loop midpoint cause the largest decrease in stability.
- A three-state model explains the thermodynamic and kinetic stability dichotomy.

## Abstract

Base pair mismatch can relieve mechanical stress in highly strained DNA molecules, but how it affects their kinetic stability is not known. Using single-molecule Fluorescence Resonance Energy Transfer (FRET), we measured the lifetimes of tightly bent DNA loops with and without base pair mismatch. Surprisingly, for loops captured by stackable sticky ends, the mismatch decreased the loop lifetime despite reducing the overall bending stress, and the decrease was largest when the mismatch was placed at the DNA midpoint. These findings show that base pair mismatch transfers bending stress to the opposite side of the loop through an allosteric mechanism known as cooperative kinking. Based on this mechanism, we present a three-state model that explains the apparent dichotomy between thermodynamic and kinetic stability of DNA loops.