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Base-pair mismatches in strained DNA loops surprisingly reduce kinetic stability. This occurs via cooperative kinking, impacting DNA loop lifetimes and stability models.

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Area of Science:

  • Molecular Biology
  • Biophysics
  • Biochemistry

Background:

  • Base-pair mismatches in DNA can alleviate mechanical stress.
  • The effect of mismatches on the kinetic stability of strained DNA is not well understood.

Purpose of the Study:

  • To investigate how base-pair mismatches affect the kinetic stability of tightly bent DNA loops.
  • To elucidate the mechanism by which mismatches influence DNA loop lifetimes.

Main Methods:

  • Single-molecule fluorescence resonance energy transfer (smFRET) was employed.
  • Measurement of DNA loop lifetimes with and without base-pair mismatches.

Main Results:

  • Mismatches decreased loop lifetimes, contrary to expectations based on reduced bending stress.
  • The largest decrease in lifetime was observed when the mismatch was at the DNA loop's midpoint.
  • Findings suggest an allosteric mechanism, cooperative kinking, where mismatches increase stress on the opposite side.

Conclusions:

  • Base-pair mismatches can destabilize DNA loops kinetically through cooperative kinking.
  • A three-state model was developed to explain the observed thermodynamic and kinetic stability.
  • This research provides new insights into DNA mechanics and stability.