UV-Induced DNA to Protein Cross-Linking in Mammalian Cells

  • Paul Todd
  • Antun Han
Chapter

Abstract

Evidence for the cross-linking of DNA to protein was discovered almost simultaneously in UV-irradiated microorganisms and mammalian cells (Smith, 1962; Alexander and Moroson, 1962). Subsequent experiments in which DNA to protein adducts were sought in mixtures of protein and DNA exposed to ultraviolet light clearly indicated that such a reaction is possible (Smith, 1962; 1964a, b; 1967; Sklobovskaya and Ryabchenko, 1970a, b). This report has two aims: first, to summarize the information indicating that DNA-protein cross-links are induced in mammalian cells by ultraviolet light, and second, to review experimental studies that attempt to correlate cross-link induction and biological damage. The demonstration of cross-linking has been done in two ways: (1) the detection of unextractable DNA in irradiated cells, and (2) the isolation and identification of specific photoproducts from irradiated cells. Correlations concerning the involvement of protein in UV-induced lethality have been made utilizing (1) action and absorption spectra, (2) the investigation of biological damage not attributable to pyrimidine dimers, (3) correlations of cross-link induction with biological effect under various experimental conditions, and (4) a search for repair processes associated with DNA-protein cross-linking.

Keywords

Mammalian Cell Ultraviolet Light Action Spectrum Chinese Hamster Cell Pyrimidine Dimer 
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References

  1. Alexander, P., and Moroson, H., 1962, Cross-linking of deoxyribonucleic acid to protein following ultra-violet irradiation of different cells, Nature 194: 882–883.PubMedCrossRefGoogle Scholar
  2. Allen, B.S., Czeto, A., and Todd, P., 1972, Comparison of ultraviolet light inactivation spectrum and absorption spectra of mammalian cells, Biophys. Soc. Abstr. 12: 12a.Google Scholar
  3. Buhl, S.N., Setlow, R.B., and Regan, J.D., 1973, Recovery of the ability to synthesize DNA in segments of normal size at long times after ultraviolet irradiation of human cells, Biophys. J. 13: 1265–1275.PubMedCrossRefGoogle Scholar
  4. Buhl, S.N., Setlow, R.B., and Regan, J.D., 1974, DNA repair in Potorous tridactylus, Biophys. J. 14: 791–803.PubMedCrossRefGoogle Scholar
  5. Chu, E.H.Y., 1965, Effects of ultraviolet radiation on mammalian cells. I. Induction of chromosome aberrations, Mutat. Res. 2: 75–94.PubMedCrossRefGoogle Scholar
  6. Cook, J.S., and Regan, J.D., 1969, Photoreactivation and photoreactivating enzyme activity in an order of mammals (Marsupialia), Nature 223: 1066–1067.PubMedCrossRefGoogle Scholar
  7. Djordjevic, B., and Djordjevic, O., 1965, Survival and chromosomal aberrations in a synchronized mammalian cell culture treated with 5-bromodeoxyuridine and irradiated by ultraviolet light, in “Progress in Biochemical Pharmacology” (R. Paoletti and R. Vertua, eds.), Vol. I, pp. 71–77, Butterworths, Washington.Google Scholar
  8. Djordjevic, B., and Szybalski, W., 1960, Genetics of human cell lines. III. Incorporation of 5-bromo, 5-iododeoxyuridine into the deoxyribonucleic acid of human cells and its effect on radiation sensitivity, J. Exp. Med. 112: 509–531.PubMedCrossRefGoogle Scholar
  9. Djordjevic, B., and Tolmach, L.J., 1967, Responses of synchronous populations of HeLa cells to ultraviolet irradiation at selected stages of the generation cycle, Radiat. Res. 32: 327–346.PubMedCrossRefGoogle Scholar
  10. Domon, M., and Rauth, A.M., 1969, Ultraviolet irradiation of mouse L cells: Effects on cells in the DNA synthesis phase, Radiat. Res. 40: 414–429.PubMedCrossRefGoogle Scholar
  11. Domon, M., and Rauth, A.M., 1973, Cell cycle specific recovery from fractionated exposures of ultraviolet light, Radiat. Res. 55: 81–92.PubMedCrossRefGoogle Scholar
  12. Erikson, R.L., and Szybalski, W., 1963, Molecular radiobiology of human cell lines. IV. Variation in ultraviolet and X-ray sensitivity during the division cycle, Radiat. Res. 18: 200–212.CrossRefGoogle Scholar
  13. Fisher, G.J., Varghese, A.J., and Johns, H.E., 1974, Ultravioletinduced reactions of thymine and uracil in the presence of cysteine, Photochem. PhotobioZ. 20: 109–120.CrossRefGoogle Scholar
  14. Habazin, V., and Han, A., 1970, Ultraviolet light-induced DNA-to-protein cross-linking in HeLa cells, Int. J. Radiat. Biol. 17: 569–575.CrossRefGoogle Scholar
  15. Han, A., 1973, Cell cycle dependent effects of ultraviolet light in mammalian cells, Stud. Biophys. 36 /37: 127–137.Google Scholar
  16. Han, A., Korbelik, M., and Ban, J., 1975, DNA-to-protein cross-linking in synchronized HeLa cells exposed to ultraviolet light, Int. J. Radiat. Biol. 27: 63–74.CrossRefGoogle Scholar
  17. Han, A., Miletic, B., and Petrovic, D., 1965, The action of ultraviolet light on repair of X-ray damage in L-cells grown in culture, Int. J. Radiat. Biol. 8: 187–190.CrossRefGoogle Scholar
  18. Han, A., and Sinclair, W.K., 1969, Sensitivity of synchronized Chinese hamster cells to ultraviolet light, Biophys. J. 9: 1171–1192.PubMedCrossRefGoogle Scholar
  19. Hyde, J.E., and Walker, I.O., 1975, Covalent cross-linking of histones in chromatin, FEBS Lett. 50: 150–158.PubMedCrossRefGoogle Scholar
  20. Johns, E.W., 1971, The preparation and characterization of histones, in “Histones and Nucleohistones” (D.M.P. Phillips, ed.), pp. 2–36, Plenum Press, London.Google Scholar
  21. Kornberg, R.D., 1974, Chromatin structure: A repeating unit of histones and DNA, Science 184: 868–871.PubMedCrossRefGoogle Scholar
  22. Kornberg, R.D., and Thomas, J.O., 1974, Chromatin structure: Oligomers of the histones, Science 184: 865–868.PubMedCrossRefGoogle Scholar
  23. Kornhauser, A., Pathak, M.A., Zimmerman, E., and Szabo, G., 1975, The in vivo effect of UV irradiation on epidermal chromatin. Abstr. Int. Symp. “Protein and Other Adducts to DNA: Their Significance to Aging, Carcinogenesis, and Radiation Biology,” Williamsburg, Virginia, May 2–6, 1975.Google Scholar
  24. Lange, C.S., Clark, R.W., and Mitchell, P., 1975, Demonstration of the protein linkages between DNA subunits and a model for the organization of DNA in the mammalian chromosome. Abstr. Int. Symp. “Protein and Other Adducts to DNA: Their Significance to Aging, Carcinogenesis, and Radiation Biology,” Williamsburg, Virginia, May 2–6, 1975.Google Scholar
  25. Loeb, J.E., 1968, Gel filtration of deoxyribonucleoprotein on agarose, Biochim. Biophys. Acta 157: 424–426.PubMedCrossRefGoogle Scholar
  26. Marmur, J., 1961, A procedure for the isolation of deoxyribonucleic acid from micro-organisms, J. Mol. BioZ. 3: 208–218.CrossRefGoogle Scholar
  27. Pathak, M.A., and Zimmerman, E., 1972, Biochemical changes in epidermal nucleic acids following U.V. irradiation, VI Int. Congr. Photobiol. Abstr. No. 044.Google Scholar
  28. Phillips, D.M.P. (ed.), 1971, “Histones and Nucleohistones,” Plenum Press, New York.Google Scholar
  29. Rauth, A.M., 1970, Effects of ultraviolet light on mammalian cells in culture, Curr. Topics Radiat. Res. 6: 197–248.Google Scholar
  30. Rauth, A.M., and Whitmore, G.F., 1966, The survival of synchronized L cells after ultraviolet irradiation, Radiat. Res. 28: 84–95.PubMedCrossRefGoogle Scholar
  31. Regan, J.D., Setlow, R.B., and Ley, R.D., 1971, Normal and defective repair of damaged DNA in human cells: A sensitive assay utilizing the photolysis of bromodeoxyuridine, Proc. Nat. Acad. Sci. USA 68: 708–712.PubMedCrossRefGoogle Scholar
  32. Robbins, E., and Borun, T.W., 1967, The cytoplasmic synthesis of histones in HeLa cells and its temporal relation to DNA replication, Proc. Nat. Acad. Sci. USA 57: 409–416.PubMedCrossRefGoogle Scholar
  33. Ryabchenko, N.I., Slobovskaya, M.V., Ivannik, B.P., and Yaskevich, A.G., 1965, UV cross-links DNA proteins, Tezisy Dokl. Nauchn, Sessi i, Inst. Med. Radiol. Akad. Nauk SSSR, ist Sb, Obninsk, pp. 24–26.Google Scholar
  34. Schott, H.N., and Shetlar, M.D., 1974, Photochemical addition of amino acids to thymine, Biochem. Biophys. Res. Commun. 59: 1112–1116.PubMedCrossRefGoogle Scholar
  35. Shetlar, M.D., and Lin, E.T., 1975, Formation of thymine-lysine adducts in irradiated DNA-lysine systems, Amer. Soc. Photobiol., Abstr. p. 115.Google Scholar
  36. Sinclair, W.K., and Morton, R.A., 1965, X-ray and ultraviolet sensitivity of synchronized Chinese hamster cells at various stages of the cell cycle, Biophys. J. 5: 1–25.PubMedCrossRefGoogle Scholar
  37. Sklobovskaya, M.V., and Ryabchenko, N.I., 1970a, Snizheniye vykhoda DNK deproteinatziyi UF-ili gamma-obluchennykh rastvorov desoxynukleoproteida. Soobshchenie I. Zavisimost’ velichiny effecta of polnot’ kompleksirovaniya DNK byelkom, Radiobiologiya 10: 14–18.Google Scholar
  38. Sklobovskaya, M.V., and Ryabchenko, N.I., 1970b, Snizheniye vykhoda DNK deproteinatziyi UF-ili gamma-obluchennykh rastvorov desoxynukleoproteida. II. Nekotorye voprosy formirovaniya povrezhdyeniya, Radiobiologiya 10: 332–337.Google Scholar
  39. Smets, L.A., and Cornelis, J.J., 1971, Repairable and irrepairable damage in 5-bromouracil-substituted DNA exposed to ultraviolet radiation, Int. J. Radiat. Biol. 19: 445–457.CrossRefGoogle Scholar
  40. Smith, K.C., 1962a, A chemical basis for the sensitization of bacteria to ultraviolet light by incorporated bromouracil, Biochem. Biophys. Res. Commun. 6: 458–463.PubMedCrossRefGoogle Scholar
  41. Smith, K.C., 1962b, Dose dependent decrease in extractability of DNA from bacteria following irradiation with ultraviolet light or with visible light plus dye, Biochem. Biophys. Res. Commun. 8: 157–163.PubMedCrossRefGoogle Scholar
  42. Smith, K.C., 1964a, Photochemistry of the nucleic acids, in “Photo-physiology” (A.C. Giese, ed.), Vol. 2, pp. 329–388, Academic Press, New York.Google Scholar
  43. Smith, K.C., 1964b, The photochemical interaction of deoxyribonucleic acid and protein in vivo and its biological importance, Photochem. Photobiol. 3: 415–427.CrossRefGoogle Scholar
  44. Smith, K.C., 1967, Biologically important damage to DNA by photo- products other than cyclobutane-type thymine dimers, in “Radiation Research” (G. Silini, ed.), pp. 756–770, North-Holland Publishing Co., Amsterdam.Google Scholar
  45. Smith, K.C., and O’Leary, M.E., 1967, Photoinduced DNA-protein cross-links and bacterial killing: A correlation at low temperatures, Science 155: 1024–1026.PubMedCrossRefGoogle Scholar
  46. Steward, D.L., and Humphrey, R.M., 1966, Induction of thymine dimers in synchronous populations of Chinese hamster cells, Nature 212: 298–300.PubMedCrossRefGoogle Scholar
  47. Todd, P., 1968, Nuclear protein thiol in cultured mammalian cells, Biochem. J. 109: 25 P.Google Scholar
  48. Todd, P., 1973, Fractionated ultraviolet light irradiation of cultured Chinese hamster cells, Radiat. Res. 55: 93–100.PubMedCrossRefGoogle Scholar
  49. Todd, P., Allen, B.S., and Hardin, J.M., 1974, A search for a nucleoprotein photoproduct in mammalian cells exposed to ultraviolet light, Amer. Soc. Photobiol., Abstr. p. 66.Google Scholar
  50. Todd, P., Allen, B.S., and Schroy, C.B., 1972, What ultraviolet-induced molecular lesions cause lethality in mammalian cells? VI Int. Congr. Photobiol. Abstr. No. 133.Google Scholar
  51. Todd, P., Coohill, T.P., Hellewell, A.B., and Mahoney, J.A., 1969, Postirradiation properties of cultured Chinese hamster cells exposed to ultraviolet light, Radiat. Res. 38: 321–339.PubMedCrossRefGoogle Scholar
  52. Todd, P., Coohill, T.P., and Mahoney, J.A., 1968, Response of cultured Chinese hamster cells to ultraviolet light of different wavelengths, Radiat. Res. 35: 390–400.PubMedCrossRefGoogle Scholar
  53. Todd, P., Schroy, C.B., and Lebed, M.R., 1973, Post-irradiation effects of photoreactivating light and caffeine on cultured marsupial cells exposed to ultraviolet light, Photochem. Photobiol. 18: 433–436.PubMedCrossRefGoogle Scholar
  54. Varghese, A.J., 1973, Properties of photoaddition products of thymine and cysteine, Biochemistry 12: 2725–2730.PubMedCrossRefGoogle Scholar
  55. Varghese, A.J., 1974, Photochemical addition of glutathione to uracil and thymine, Photochem. PhotobioZ. 20: 339–343.CrossRefGoogle Scholar
  56. Varghese, A.J., and Rauth, A.M., 1974, Evidence for the addition of sulfhydryl compounds to thymine in UV-irradiated mammalian cells. Amer. Soc. Photobiol., Abstr. p. 65.Google Scholar
  57. Williams, J.R., and Little, J.B., 1971, Correlation of intracellular UV-dose absorption with survival in cultured human cells, Radiat. Res. 47: 248–249.Google Scholar
  58. Williams, J.R., and Little, J.B., 1972, Relationship of cell size and cell conformation to the UVL survival of synchronous cultures of human cells, Radiat. Res. 51: 450.Google Scholar
  59. Zirkle, R.E., and Uretz, R.B., 1963, Action spectrum for paling (decrease in refractive index) of ultraviolet-irradiated chromosome segments, Proc. Nat. Acad. Sci. USA 49: 45–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1976

Authors and Affiliations

  • Paul Todd
    • 1
  • Antun Han
    • 2
  1. 1.Department of BiophysicsThe Pennsylvania State UniversityUSA
  2. 2.Division of Biological and Medical ResearchArgonne National LaboratoryArgonneUSA

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