Excision Repair of Bulky Lesions in the DNA of Mammalian Cells

  • R. B. Setlow
  • Eleanor Grist
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 40)


Although the excision of pyrimidine dimers from UV-irradiated human cells has been known since 1968 (1) and excision has been the subject of a number of symposia and recent reviews (2–4), the details of the process still elude us. We assume that the excision of pyrimidine dimers is of the nucleotide excision type, (a) by analogy with bacteria, (b) because it is of the large patch type, (c) because although few single strand breaks accumulate during excision in normal human cells, the numbers that accumulate in excision defective cells are much less, (d) because the introduction of an exogenous UV endonuclease enhances repair and survival in excision defective cells and (e) because inhibitors of the polymerization steps such as hydroxyurea and cytosine arabinoside result in the accumulation of single strand breaks (5, 6). (However, the number of breaks observed is much less than the number of dimers removed in uninhibited cells, indicating that the various steps in excision repair act as if they are linked to one another (7).) The various measures of excision repair of pyrimidine dimers — the best studied lesion to date because they are easy to identify and measure in a number of ways — give general agreeement (8)but different investigators obtain conflicting results in details such as the dependence on time, dose and the method of measurement (9–11). Nevertheless, the various techniques indicate that excision repair of dimers varies widely among cell lines and strains. For example, rodent cells are low excisers compared to normal human cells (12), and among humans the cells of most of the individuals with xeroderma pigmentosum (XP) are defective in excision repair (13).


Excision Repair Single Strand Break Xeroderma Pigmentosum Ataxia Telangiectasia Pyrimidine Dimer 
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  1. 1.
    J. D. Regan, J. E. Trosko, and W. L. Carrver, Evidence for excision of ultraviolet induced pyrimidine dimers from the DNA of human cells in vitro, Biophys. J. 8: 319 (1968).PubMedCrossRefGoogle Scholar
  2. 2.
    P. C. Hanawalt, E. C. Friedberg, and C. F. Fox, editors, “DNA Repair Mechanisms,” Academic Press, N. Y. (1978).Google Scholar
  3. 3.
    L. Grossman, A. Braun, R. Feldberg, and I. Mahler, Enzymatic repair of DNA, Ann. Rev. Biochem. 44: 19 (1975).PubMedCrossRefGoogle Scholar
  4. 4.
    P. C. Hanawalt, P. K. Cooper, A. K. Ganesan, and C. A. Smith, DNA repair in bacteria and mammalian cells, Ann. Rev. Biochem. 48: 783 (1979).PubMedCrossRefGoogle Scholar
  5. 5.
    A. R. S. Collins, S. L. Schor, and R. T. Johnson, The inhibition of repair in UV irradiated human cells, Mutat. Res. 42: 413 (1977).PubMedCrossRefGoogle Scholar
  6. 6.
    W. C. Dunn and J. D. Regan, Inhibition of DNA excision repair in human cells by arabinofuranosyl cytosine: effect on normal and xeroderma pigmentosum cells, Molec. Pharmacol. 15: 367 (1979).Google Scholar
  7. 7.
    R. B. Setlow and E. Grist, unpublished observation.Google Scholar
  8. 8.
    F. E. Ahmed and R. B. Setlow, DNA repair in xeroderma pigmentosum cells treated with combinations of ultraviolet radiation and N-acetoxy-2-acetylaminofluorene, Cancer Res. 39: 471 (1979).PubMedGoogle Scholar
  9. 9.
    J. I. Williams and J. E. Cleaver, Excision repair of ultraviolet damage in mammalian cells. Evidence for two steps in the excision of pyrimidine dimers, Biophys. J. 22: 265 (1978).PubMedCrossRefGoogle Scholar
  10. 10.
    U. K. Ehmann, K. H. Cook, and E. C. Friedberg, The kinetics of thymine dimer excision in ultraviolet irradiated human cells, Biophys. J. 22: 249 (1978).PubMedCrossRefGoogle Scholar
  11. 11.
    F. E. Ahmed and R. B. Setlow, Kinetics of DNA repair in ultraviolet irradiated and N-acetoxy-2-acetylaminofluorene-treated mammalian cells, Biophys J. 24: 665 (1978).PubMedCrossRefGoogle Scholar
  12. 12.
    R. W. Hart and R. B. Setlow, Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species, Proc. Natl. Acad. Sci. USA 71: 2169 (1974).PubMedCrossRefGoogle Scholar
  13. 13.
    E. C. Friedberg, U. K. Ehmann, and J. I. Williams, Human diseases associated with defective DNA repair, Adv. Radiat. Biol. 8: 85 (1979).Google Scholar
  14. 14.
    R. B. Setlow and F. E. Ahmed, DNA repair in human cells exposed to combinations of carcinogenic agents, in: 13th Jerusalem Symposium on Carcinogenesis: fundamental mechanisms and environmental effects, D. Reidel, Dordrecht (1980).Google Scholar
  15. 15.
    J. E. Cleaver, Nucleosome structure controls rates of excision repair in DNA of human cells, Nature 270: 451 (1977).PubMedCrossRefGoogle Scholar
  16. 16.
    M. J. Smerdon, M. B. Kastan, and M. W. Lieberman, Distribution of repair incorporated nucleotides and nucleosome rearrangement in the chromatin of normal and xeroderma pigmentosum fibroblasts, Biochemistry 18: 3732 (1979).PubMedCrossRefGoogle Scholar
  17. 17.
    F. E. Ahmed and R. B. Setlow, Saturation of DNA repair in mammalian cells, Photochem. Photobiol. 29: 983 (1979).PubMedCrossRefGoogle Scholar
  18. 18.
    D. A. Scudiero, Decreased DNA repair synthesis and defective colony-forming ability of ataxia telangiectasia fibroblast cell strains treated with N-methyl-N’-nitro-N-guanidine, Cancer Res. 40: 984 (1980).PubMedGoogle Scholar
  19. 19.
    F. E. Ahmed and R. B. Setlow, Excision repair in ataxia telangiectasia, Fanconi’s anemia, Cockayne syndrome, and Bloom’s syndrome after treatment with ultraviolet radiation and N-acetoxy-2-acetylaminofluorene, Biochim. Biophys. Acta. 521: 805 (1978).PubMedGoogle Scholar
  20. 20.
    A. J. Brown, T. H. Fickel, J. E. Cleaver, P. H. M. Lohman, M. H. Wade, and R. Waters, Overlapping pathways for repair of damage from ultraviolet light and chemical carcinogens in human fibroblasts, Cancer Res. 39: 2522 (1979).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • R. B. Setlow
    • 1
  • Eleanor Grist
    • 1
  1. 1.Biology DepartmentBrookhaven National LaboratoryUptonUSA

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