Thymine Dimer-Induced Structural Changes to the DNA Duplex Examined with Reactive Probes
Open accessAbstract
Despite significant progress in the past decade, questions still remain about the complete structural, dynamic, and thermodynamic effect of the cis-syn cyclobutane pyrimidine dimer lesion (hereafter called the thymine dimer) on double-stranded genomic DNA. We examined a 19-mer oligodeoxynucleotide duplex containing a thymine dimer lesion using several small, base-selective reactive chemical probes. These molecules probe whether the presence of the dimer causes the base pairs to be more accessible to the solution, either globally or adjacent to the dimer. Though all of the probes confirm that the overall structure of the dimer-containing duplex is conserved compared to that of the undamaged parent duplex, reactions with both diethyl pyrocarbonate and Rh(bpy)(2)(chrysi)(3+) indicate that the duplex is locally destabilized near the lesion. Reactions with potassium permanganate and DEPC hint that the dimer-containing duplex may also be globally more accessible to the solution through a subtle shift in the double-stranded DNA ↔ single-stranded DNA equilibrium. To begin to distinguish between kinetic and thermodynamic effects, we determined the helix melting thermodynamic parameters for the dimer-containing and undamaged parent duplexes by microcalorimetry and UV melting. The presence of the thymine dimer causes this DNA duplex to be slightly less stable enthalpically but slightly less unstable entropically at 298 K, causing the overall free energy of duplex melting to remain unchanged by the dimer lesion within the error of the experiment. Here we consider these results in the context of what has been learned about the thymine dimer lesion from NMR, X-ray crystallographic, and molecular biological methods.
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Rumora et al. examined thymine dimer-induced structural changes in the DNA duplex using small base-selective reactive chemical probes.
“Recently, Rumora et al. [82] have examined the thymine dimer-induced structural changes to the DNA duplex with several small, base-selective reactive chemical probes.”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [82]
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- Authors
- Rumora, A. E., Kolodziejczak, K. M., Malhowski Wagner, A., & Núñez, M. E.
- Affiliations
- Mount Holyoke College (US)
- Department of Chemistry, Mount Holyoke College, South Hadley, Massachusetts 01075
- Corresponding author
- Núñez, Megan E.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-11-12
- Volume
- 47
- Issue
- 49
- Pages
- 13026-13035
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC2891882
- OpenAlex
- W2032536992
- Cited by
- 18
- References
- 41
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2021: 3 · 2020: 3 · 2018: 1 · 2017: 1 · 2013: 1
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R15GM083250)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Keywords
- thymine dimers, cyclobutane pyrimidine dimers, DNA duplex structure, DNA damage, diethylpyrocarbonate, potassium permanganate, DEPC, helix stability
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