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Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair
Published on: May 24, 2017
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Photoinduced charge separation and DNA self-repair depend on sequence directionality and stacking pattern
Corinna L Kufner1, Sarah Crucilla1,2, Dian Ding3,4
1Department of Astronomy, Harvard-Smithsonian Center for Astrophysics 60 Garden Street Cambridge MA 02138 USA corinna.kufner@cfa.harvard.edu.
Chemical Science
|February 9, 2024
Summary
The TTAG DNA sequence self-repairs cyclobutane pyrimidine dimers (CPDs) more efficiently than GATC due to favorable base stacking. This DNA repair mechanism is conformation-dependent, influencing electron transfer and photostability.
Area of Science:
- Photochemistry
- DNA Damage and Repair
- Computational Biophysics
Background:
- UV light absorption induces charge separation in DNA, a key step in DNA damage.
- Specific DNA sequences, like GATC, can undergo self-repair of cyclobutane pyrimidine dimers (CPDs) via sequential electron transfer.
- The efficiency of this self-repair is influenced by nucleobase redox potentials and sequence-dependent stacking.
Purpose of the Study:
- To compare the CPD self-repair efficiency of the TTAG sequence with the previously studied GATC sequence.
- To elucidate the molecular mechanisms underlying the observed differences in self-repair quantum yields.
- To investigate the role of DNA conformation and alternative photodeactivation pathways in photoinduced electron transfer for DNA repair.
Main Methods:
- UV-irradiation experiments were conducted to measure CPD formation and self-repair yields.
- Molecular dynamics (MD) simulations were employed to model DNA conformational dynamics.
- Quantum mechanics/molecular mechanics (QM/MM) calculations were used to analyze electronic states and energy landscapes.
Main Results:
- The TTAG sequence exhibited higher CPD self-repair quantum yields (0.58 ± 0.23%) compared to GATC (0.44 ± 0.18%).
- A photostationary equilibrium favoring self-repair was reached at higher percentages for TTAG (40 ± 16%) than for GATC (33 ± 13%).
- Enhanced stacking overlap between Guanine (G) and Adenine (A) in TTAG lowers the energy of the A⁻˙G⁺˙ charge transfer state, facilitating repair.
Conclusions:
- DNA sequence conformation significantly impacts photoinduced electron transfer efficiency and DNA self-repair.
- Alternative photorelaxation pathways compete with the electron transfer mechanism, affecting overall repair efficiency.
- Understanding these mechanisms allows for the prediction of DNA sequences with enhanced electron transfer and photostability, relevant to early Earth photochemistry.
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