Cited by 96DNA and Nucleic Acid ChemistryDNA Repair MechanismsCarcinogens and Genotoxicity Assessment

Inter-strand photoproducts are produced in high yield within A-DNA exposed to UVC radiation

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Douki, T.·2003·Nucleic Acids Research

Abstract

Far-UV irradiation of DNA leads to the dimerization of pyrimidine bases, resulting in the formation of cyclobutane type dimers and (6-4) photoproducts. In the dry state, an additional thymine dimeric photolesion, the spore photoproduct, is also generated. While most photoproducts are expected to be produced between adjacent pyrimidines, little attention has been paid to lesions involving bases located on different DNA strands. Using HPLC- mass spectrometry analysis of enzymatically digested DNA, we observed that, in the dry state, inter-strand dimeric photoproducts represented 30% of the total yield of dimeric thymine lesions. The major inter-strand damage was found to be the spore photoproduct. Formation of inter-strand lesions in significant yield could be obtained in solution upon modification of the DNA conformation as the result of the addition of large amounts of ethanol. In both cases, DNA is in the A-form, which is characterized by a high compaction, likely to favor inter-strand photoreactions. Since the latter DNA conformation is also predominant in bacterial spores, the formation and repair of dimeric photoproducts involving thymine bases located on different DNA strands may thus be relevant in terms of deleterious effects of UV radiation to the latter microorganisms.

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Crossref · 10.1093/nar/gkg408

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  • Biologically relevant CPDs involve adjacent bases.

    “Although interstrand photoproducts can be obtained under very specific conditions within isolated DNA (46), the biologically relevant CPDs involve adjacent bases.”
  • The yield of UVA-induced CPDs is larger than that of oxidatively generated lesions such as 8-oxoGua.

    “As a striking information, the yield of CPDs was found to be larger than that of oxidatively generated lesions such as 8-oxoGua (32,46,61,88) that were long thought to be the hallmark of UVA genotoxicity, as further discussed below.”
  • Neither 6-4PPs nor Dewar valence isomers have been observed by specific chromatographic techniques after UVA exposure, even at high doses.

    “Although tiny amounts of 6-4PPs have been detected by immunological assays (55), neither the formation of this class of damage nor of DEWs has been observed using more specific chromatographic techniques, even at high doses of UVA (46,61,88).”

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Research works printed but not linked: 6

  1. [1]Cadet J. and Vigny,P. (1990) Photochemistry of nucleic acids. In Morrison,H. (ed.), Bioorganic Photochemistry. Wiley, New York, NY, Vol. 1, pp. 1–272.
  2. [2]Douki T. and Cadet,J. (1995) UV and nucleic acids. In Jornvall,H. and Jollès,P. (eds), Interface between Chemistry and Biochemistry. Birkhauser Verlag, Basel, Switzerland, pp. 173–197.
  3. [8]Douki T., Court,M., Sauvaigo,S., Odin,F. and Cadet,J. (2000) Formation of the main UV-induced thymine dimeric lesions within isolated and cellular DNA as measured by HPLC-MS/MS. J. Biol. Chem., 275, 11678–11685. [DOI] [PubMed] [Google Scholar]
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  6. [27]Ravanat J.-L., Douki,T., Incardona,M.-F. and Cadet,J. (1993) HPLC separations of normal and modified nucleobases and nucleosides on an amino silica gel column. J. Liquid Chromatogr., 16, 3185–3202. [Google Scholar]

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Authors
Douki, T.
Affiliations
Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
Corresponding author
Douki, T.
Venue
Nucleic Acids Research
Published
2003-06-15
Volume
31
Issue
12
Pages
3134-3142
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2135305503
Cited by
96
References
58
Citations by year
2026: 3 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 6 · 2013: 4 · 2012: 6
FWCI
2.19
Type
journal article
Language
en
Open access
Locations
  • Nucleic Acids Research (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
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 › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
spore photoproduct, UV-C radiation, thymine dimers, cyclobutane dimers, 6-4 photoproducts, DNA conformation, ethanol, bacterial spores, UV damage
MeSH terms
Chromatography, High Pressure Liquid, DNA, DNA Damage, Nucleic Acid Conformation, Pyrimidine Dimers, Mass Spectrometry, Thymidine, Ultraviolet Rays

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