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Oxidative Damage: DNA Repair and Inducible Resistance

  • Bruce Demple
  • Yasmin Daikh
  • Jean Greenberg
  • Arlen Johnson

Abstract

Free radicals and activated oxygen species are generated in a variety of ways. For example, most of the biological effects of ionizing radiations can be ascribed to the oxygen radicals they produce, such as superoxide anion (O2 \(\overline \bullet \)) and hydroxyl radical (·OH) (1). Such radicals are also produced deliberately by macrophages during inflammatory responses, evidently as a means of destroying invading cells (2). It seems likely that the normal reduction of O2 to water by cytochrome C oxidase might inadvertently release intracellular activated oxygen. Indeed, bacteria devoid of superoxide dismutase, which destroys O2 \(\overline \bullet \), display a strongly increased spontaneous mutation frequency in aerated but not in hypoxic culture (3). This apparent production of oxygen radicals under normal aerobic conditions underscores the need to understand the nature of the cellular defenses against oxidative damage. We are investigating the mechanisms that cells employ to avert oxidative damage and to correct such damage when it does occur.

Keywords

Ataxia Telangiectasia Cumene Hydroperoxide Hypoxic Culture Alkyl Hydroperoxide Reductase Spontaneous Mutation Frequency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    F. Hutchinson, Chemical changes induced in DNA by ionizing radiation. Prog. Nucl. Acids Res. Mol. Biol. 32, 115–154 (1985).CrossRefGoogle Scholar
  2. 2.
    P. I. Fields, R. V. Swanson, C. G. Haidaris and F. Heffron, Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc. Natl. Acad. Sci. (USA) 5189–5193 (1986).Google Scholar
  3. 3.
    S. B. Farr, R. D’Ari and D. Touati, Oxygen-dependent mutagenesis in Escherichia coli lacking superoxide dismutase. Proc. Natl. Acad. Sci. (USA) 83, 8268–8272 (1986).CrossRefGoogle Scholar
  4. 4.
    T. Noguti and T. Kada, Studies on DNA repair in Bacillus subtilus: II. Partial purification and mode of action of an enzyme enhancing the priming activity of gamma-irradiated DNA. Biochem. Biophys. Acta 395, 294–305 (1975).PubMedGoogle Scholar
  5. 5.
    B. Demple, J. Halbrook and S. Linn, Escherichia coli xth mutants are hypersensitive to hydrogen peroxide. J. Bacteriol. 153, 1079–1083 (1983).PubMedGoogle Scholar
  6. 6.
    B. Demple, A. Johnson and D. Fung, Exonuclease III and endonuclease IV remove 3’ blocks from DNA synthesis primers in H2O2-damaged Escherichia coli. Proc. Natl. Acad. Sci. (USA) 7731–7735 (1986).Google Scholar
  7. 7.
    H. R. Warner, B. Demple, W. A. Deutsch, C. M. Kane, and S. Linn, Apurinic/ apyrimidinic endonucleases in repair of pyrimidine dimers and other lesions in DNA. Proc. Natl. Acad. Sci. (USA) 77, pp. 4602–4606 (1980).CrossRefGoogle Scholar
  8. 8.
    R. P. Cunningham, S. M. Saporito, S. G. Spitzer and B. Weiss, An Endonuclease IV (nfo) mutant of Escherichia coli. J. Bacteriol. 168, 1120-1127 (1986).Google Scholar
  9. 9.
    S. Linn. The deoxyribonucleases of Escherichia coli. In Nucleases (S. Linn and R. J. Roberts, Eds.) pp. 291–310. Cold Spring Harbor Laboratory, New York (1985).Google Scholar
  10. 10.
    C. M. Kane and S. Linn, Purification and characterization of a apurinic/apyrimidinic endonuclease from HeLa cells. J. Biol. Chem. 256, 3405–3414 (1981).PubMedGoogle Scholar
  11. 11.
    B. Demple and J. Halbrook, Inducible repair of oxidative DNA damage in Escherichia coli. Nature (London) 304, 466–468 (1983).CrossRefGoogle Scholar
  12. 12.
    J. T. Greenberg and B. Demple, Glutathione in Escherichia coli is dispensable for resistance to H2O2 and ionizing radiation. J. Bacteriol. 169, 1026–1029 (1986).Google Scholar
  13. 13.
    I R. A. VanBogelen, P. M. Kelley and, F. C. Neidhardt, Differential induction of heat shock, SOS, and oxidation stress régulons and accumulation of nucleotides in Escherichia coli. J. Bacteriol. 169, 26–32 (1987).Google Scholar
  14. 14.
    M. F. Christman, R. W. Morgan, F. S. Jacobson and B. N. Ames, Positive control of a regulon for defenses against oxidative stress and some heat shock proteins in Salmonella typhimurium. Cell 41, 753–762 (1985).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Bruce Demple
    • 1
  • Yasmin Daikh
    • 1
  • Jean Greenberg
    • 1
  • Arlen Johnson
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyHarvard UniversityCambridgeUSA

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