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Cited by 338DNA and Nucleic Acid ChemistryFree Radicals and AntioxidantsDNA Repair Mechanisms

Oxidation of DNA: Damage to Nucleobases

Kanvah, Sriram, Joseph, Joshy, Schuster, Gary B., Barnett, Robert N., Cleveland, Charles L., Landman, Uzi·2010·Accounts of Chemical Research
DOI 10.1021/ar900175a
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Abstract

All organisms store the information necessary to maintain life in their DNA. Any process that damages DNA, causing a loss or corruption of that information, jeopardizes the viability of the organism. One-electron oxidation is such a process. In this Account, we address three of the central features of one-electron oxidation of DNA: (i) the migration of the radical cation away from the site of its formation; (ii) the electronic and structural factors that determine the nucleobases at which irreversible reactions most readily occur; (iii) the mechanism of reaction for nucleobase radical cations. The loss of an electron (ionization) from DNA generates an electron "hole" (a radical cation), located most often on its nucleobases, that migrates reversibly through duplex DNA by hopping until it is trapped in an irreversible chemical reaction. The particular sequence of nucleobases in a DNA oligomer determines both the efficiency of hopping and the specific location and nature of the damaging chemical reaction. In aqueous solution, DNA is a polyanion because of the negative charge carried by its phosphate groups. Counterions to the phosphate groups (typically Na(+)) play an important role in facilitating both hopping and the eventual reaction of the radical cation with H(2)O. Irreversible reaction of a radical cation with H(2)O in duplex DNA occurs preferentially at the most reactive site. In normal DNA, comprising the four common DNA nucleobases G, C, A, and T, reaction occurs most commonly at a guanine, resulting in its conversion primarily to 8-oxo-7,8-dihydroguanine (8-OxoG). Both electronic and steric effects control the outcome of this process. If the DNA oligomer does not contain a suitable guanine, then reaction of the radical cation occurs at the thymine of a TT step, primarily by a tandem process. The oxidative damage of DNA is a complex process, influenced by charge transport and reactions that are controlled by a combination of enthalpic, entropic, steric, and compositional factors. These processes occur over a broad distribution of energies, times, and spatial scales. The emergence of a complete picture of DNA oxidation will require additional exploration of the structural, kinetic, and dynamic properties of DNA, but this Account offers insight into key elements of this challenge.

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  • The distribution of Type I oxidative damage is modulated, with enhanced guanine specificity due to charge transfer within DNA.

    “The distribution of oxidatively generated damage involving Type I photosensitization has been shown to be modulated, leading to an enhanced guanine specificity by the occurrence of charge transfer within DNA (104,105).”

    From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [105]

  • A lack of repair of guanine oxidized to 8-oxo-7,8-dihydroguanine (8-oxoG) can also result in an increased number of G-to-A transitions (depending on the sequence context) but normally results in an abundance of G-to-T transversions.

    “A lack of repair of guanine oxidized to 8-oxo-7,8-dihydroguanine (8-oxoG) can also result in an increased number of G-to-A transitions (depending on the sequence context) but normally results in an abundance of G-to-T transversions”

    From Mismatch Repair of DNA Replication Errors Contributes to Microevolution in the Pathogenic Fungus <i>Cryptococcus neoformans</i> (2017) · cites this paper as [27]

  • Minor or no phenotypes are expected on ROS as oxidative damage is mainly repaired by the base excision repair (BER) pathway, although MMR has been shown to play a role in repairing oxidation of guanine to 8-oxo-7,8-dihydroguanine (8-oxoG).

    “Minor or no phenotypes are expected on ROS as oxidative damage is mainly repaired by the base excision repair (BER) pathway, although MMR has been shown to play a role in repairing oxidation of guanine to 8-oxo-7,8-dihydroguanine (8-oxoG) (27).”

    From Mismatch Repair of DNA Replication Errors Contributes to Microevolution in the Pathogenic Fungus <i>Cryptococcus neoformans</i> (2017) · cites this paper as [27]

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Authors
Kanvah, S., Joseph, J., Schuster, G. B., Barnett, R. N., Cleveland, C. L., & Landman, U.
Affiliations
Georgia Institute of Technology (US)
Corresponding author
  • Schuster, Gary B.
  • Landman, Uzi
ORCID
Venue
Accounts of Chemical Research
Publisher
American Chemical Society (ACS)
Published
2009-11-25
Volume
43
Issue
2
Pages
280-287
ISSN
  • 0001-4842 (ISSN-L)
  • 1520-4898
DOI
10.1021/ar900175a
OpenAlex
W2068888525
Cited by
338
References
42
Citations by year
2026: 6 · 2025: 15 · 2024: 12 · 2023: 18 · 2022: 24 · 2021: 21 · 2020: 23 · 2019: 20 · 2018: 9 · 2017: 23 · 2016: 27 · 2015: 29 · 2014: 29 · 2013: 25 · 2012: 23
FWCI
7.64
Type
journal article
Language
en
Open access
closed
Locations
  • Accounts of Chemical Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
DNA oxidation, one-electron oxidation, radical cations, charge migration, guanine oxidation, 8-oxo-7,8-dihydroguanine, tandem oxidation, thymine oxidation, counterion effects, steric effects, electronic effects
MeSH terms
DNA, DNA Damage, Free Radicals, Models, Molecular, Nucleic Acid Conformation, Oxidation-Reduction, Purines, Pyrimidines

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