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Single-Base Lesions and Mismatches Alter the Backbone Conformational Dynamics in DNA

M N Westwood1, K D Ljunggren1, Benjamin Boyd1

  • 1Department of Chemistry, Missouri State University, 901 South National Avenue, Springfield, Missouri 65897, United States.

Biochemistry
|March 10, 2021
PubMed

Insights

DNA damage, like lesions and mismatches, alters DNA backbone dynamics. These conformational changes are crucial for DNA repair enzymes to recognize and bind damaged DNA sites.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Structural Biology

Background:

  • DNA damage is linked to diseases such as cancer and aging.
  • DNA glycosylases initiate base excision repair by recognizing damaged DNA.
  • Altered DNA dynamics may facilitate lesion recognition by repair enzymes.

Purpose of the Study:

  • To quantify changes in DNA backbone conformational dynamics caused by single-base lesions and mismatches.
  • To investigate the role of these dynamic alterations in DNA repair enzyme binding and specificity.

Main Methods:

  • Solution nuclear magnetic resonance (NMR) spectroscopy was employed.
  • Quantification of BI-BII backbone conformational dynamics in DNA containing uracil, dihydrouracil, 1,N6-ethenoadenine, and T:G mismatches.

Main Results:

  • Stepwise alterations in the %BII and Gibbs free energy (ΔG) of the BI-BII dynamic equilibrium were observed in damaged DNA.
  • The dynamic equilibrium shifted towards endothermicity for phosphates near the lesion or mismatch.
  • Significant alterations in phosphates correlated with sites critical for DNA repair enzyme binding.

Conclusions:

  • Local conformational rearrangements in the DNA backbone are induced by single-base lesions and mismatches.
  • These dynamic changes likely play a significant role in the recognition of damaged DNA by repair enzymes.
  • Understanding these dynamics can provide insights into DNA repair mechanisms and disease pathogenesis.

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