Advertisement

Enzymatic Studies of Base Excision Repair in Cultured Human Fibroblasts and in Escherichia coli

  • Stuart Linn
  • Bruce Demple
  • Dale W. Mosbaugh
  • Huber R. Warner
  • Walter A. Deutsch
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 40)

Abstract

With the discovery some six years ago of uracil DNA glycosylase by Lindahl,1 it became possible to define a new mode of excision repair, “base excision repair,”2 which was hypothesized to occur by (i) removal of a DNA base by hydrolysis of the glycosylic bond, (ii) cleavage of a phosphodiester bond adjacent to the resulting apurinic/ apyrimidinic (AP) site by an “AP endonuclease,” and (iii) subsequent excision of the sugar and resynthesis by DNA polymerase. In the past few years it has been the goal of our laboratory to study the base-excision processes in depth in order to determine exactly the sequence and mechanisms of the enzymatic events involved, and the relation of this repair mode to nucleotide excision repair processes. This article summarizes some of the recent studies from our laboratory toward this goal. Space considerations prevent a review of related studies from other laboratories and such an omission should not be taken to indicate that our results are particularly unique. Indeed we encourage the reader to consult articles on similar endeavors that are found elsewhere in this volume as well as to consult Lindahl’s recent comprehensive review.3

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literature Cited

  1. 1.
    T. Lindahl, An N-glycosidase from Escherichia coli that releases free uracil from DNA containing deaminated’cytosine residues, Proc. Natl. Acad. Sci. USA 71: 3649 (1974).CrossRefGoogle Scholar
  2. 2.
    S. Linn, Workshop summary: enzymology of base excision repair, In: “DNA Repair Mechanisms,” P. C. Hanawalt, E. C. Friedberg, C. F. Fox, eds., Academic Press, New York (1978).Google Scholar
  3. 3.
    T. Lindahl, DNA glycosylases, endonucleases for apurinic/ apyrimidinic sites, and base excision repair, Prog. Nucl. Acid Res. and Mol. Biol 22: 135 (1979).CrossRefGoogle Scholar
  4. 4.
    F. T. Gates III and S. Linn, An endonuclease from Escherichia coli that acts specifically upon duplex DNA damaged by ultraviolet light, osmium tetroxide, acid, or x-rays, J. Biol. Chem. 252: 2802 (1977).PubMedGoogle Scholar
  5. 5.
    B. Demple and S. Linn, DNA N-glycosylases and UV repair, Nature, in press (1980).CrossRefGoogle Scholar
  6. 6.
    H. R. Warner, B. F. Demple, W. A. Deutsch, C. M. Kane, and S. Linn, Apurinic/apyrimidinic endonucleases in the repair of pyrimidine dimers and other lesions in DNA, Proc. Natl. Acad. Sci. USA 77, in press (1980).Google Scholar
  7. 7.
    L. Grossman, S. Riazuddin, W. Haseltine, and K. Lindan, Nucleo- tide excision repair of damaged DNA, Cold Spr. Symp. Quant. Biol. 43: 947 (1978).CrossRefGoogle Scholar
  8. 8.
    S. Linguist, A new endonuclease from Escherichia colt acting at apurinic sites in DNA, J. Biol. Chem. 252: 2808 (1977).Google Scholar
  9. 9.
    B. Weiss, S. G. Rogers, and A F. Taylor, The endonuclease activity of exonuclease III and the repair of uracil-containing DNA in Escherichia coli, In: “DNA Repair Mechanisms,” P. C. Hanawalt, E. C. Friedberg, C. F. Fox, eds., Academic Press, New York (1978).Google Scholar
  10. 10.
    W. S. Linsley, E. E. Penhoet, and S. Linn, Human endonuclease specific for apurinic/apyrimidinic sites in DNA. Partial purification and characterization of multiple forms in placenta, J. Biol. Chem. 252: 1235 (1977).PubMedGoogle Scholar
  11. 11.
    U. Kuhnlein, E. E. Penhoet, and S. Linn, An altered apurinic DNA endonuclease activity in group A and group D xeroderma pigmentosum fibroblasts, Proc. Natl. Acad. Sci. USA 73: 1169 (1976).Google Scholar
  12. 12.
    U. Kuhnlein, B. Lee, E. E. Penhoet, and S. Linn, Xeroderma pigmentosum fibroblasts of the D group lack an apurinic endonuclease species with a low apparent Km, Nucl. Acid Res. 5: 951 (1978).CrossRefGoogle Scholar
  13. 13.
    D. W. Mosbaugh and S. Linn, Further characterization of human fibroblast apurinic/apyrimidinic DNA endonucleases: the definition of two mechanistic classes of enzyme, Submitted for publication (1980).Google Scholar
  14. 14.
    A. D. Andrews, S. F. Barrett, and J. H. Robbins, Xeroderma pigmentosum neurological abnormalities correlate with colony-forming ability after ultraviolet irradiation, Proc. Natl. Acad. Sci. USA 75: 1984 (1978).CrossRefGoogle Scholar
  15. 15.
    K. Minton, M. Durphy, R. Taylor, and E. C. Friedberg, The ultraviolet endonuclease of bacteriophage T4, J. Biol. Chem. 250: 2823 (1975).PubMedGoogle Scholar
  16. 16.
    S. Yosuda and M. Sekiguchi, Further purification and characterization of T4 endonuclease V, Biochim. Biophys. Acta 442: 197 (1976).Google Scholar
  17. 17.
    K. Goldman and E. C. Friedberg, Measurement of thymine dimers in DNA by thin layer chromatography, Anal. Biochem. 53: 124 (1973).Google Scholar
  18. 18.
    W. A. Deutsch and S. Linn, DNA binding activity from cultured human fibroblasts that is specific for partially depurinated DNA and that inserts purines into apurinic sites, Proc. Natl. Acad. Sci. USA 76: 141 (1979).CrossRefGoogle Scholar
  19. 19.
    W. A. Deutsch and S. Linn, Further characterization of a DNA-purine base insertion activity from cultured human fibroblasts, J. Biol. Chem. 254: 12099 (1979).PubMedGoogle Scholar
  20. 20.
    J. A. McDonald and W. N. Kelley, Lesch-nyhan syndrome: altered kinetic properties of mutant enzyme, Science 171: 689 (1971).CrossRefGoogle Scholar
  21. 21.
    G. C. Mills, F. C. Schmalsteig, K. B. Trimmer, A. S. Goldman, and R. M. Goldblum, Purine metabolism in adenosine deaminase deficiency, Proc. Natl. Acad. Sci. USA 73: 2867 (1976).CrossRefGoogle Scholar
  22. 22.
    H. Hennings and D. Michael, Guanine-specific DNA repair after treatment of mouse skin cells with N-methyl-N’-nitro-Nnitrosoguanidine, Cancer Res. 36: 2321 (1976).PubMedGoogle Scholar
  23. 23.
    R. D. Kudrna, J. Smith, S. Linn, and E. E. Penhoet, Survival of apurinic SV40 DNA in the D complementation group of xeroderma pigmentosum, Mut. Res. 62: 173 (1979).CrossRefGoogle Scholar
  24. 24.
    Z. Livneh, D. Elad, and J. Sperling, Enzymatic insertion of purine bases into depurinated DNA in vitro, Proc. Natl. Acad. Sci. USA 76: 1089 (1979).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Stuart Linn
    • 1
  • Bruce Demple
    • 1
  • Dale W. Mosbaugh
    • 1
  • Huber R. Warner
    • 1
  • Walter A. Deutsch
    • 1
  1. 1.Department of BiochemistryUniversity of CaliforniaBerkeleyUSA

Personalised recommendations