Advertisement

In Vitro Repair of Cisplatin-Dna Adducts by a Defined Enzyme System

  • J. D. Page
  • I. Husain
  • S. G. Chaney
  • A. Sancar
Part of the Developments in Oncology book series (DION, volume 54)

Abstract

It is now well established that DNA is the target for the cytotoxic effects of platinum anticancer drugs (1). There are molecular mechanisms that remove the Pt adducts from DNA and thus reverse the biological effects of the Pt drugs. These DNA repair mechanisms have been characterized in E. coli. Of particular interest is the nucleotide excision because this pathway has been shown to be the major repair pathway responsible for cis-DDP resistance of this organism (2). Nucleotide excision repair in E. coli is mediated by ABC excision nuclease (excinuclease) which is composed of three subunits, the UvrA, UvrB and UvrC proteins. The enzyme incises on both sides of the modified nucleotide(s) hydrolyzing the 8th phosphodiester bond 5′ (7 bases 5′) and the 4th or 5th phosphodiester bond 3′ (3 or 4 bases 3′) to the adduct (3). Thus it removes a little over one turn of DNA from the damaged strand. The resulting gap is filled in by DNA polymerases and sealed by ligase.

Keywords

Nucleotide Excision Repair Phosphodiester Bond Carrier Ligand Platinum Anticancer Drug UvrC Protein 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Pinto, A.L. and Lippard, S.J. (1985) Biochim. Biophys. Acta 780, 167–180.PubMedGoogle Scholar
  2. 2.
    Beck, D.J. and Brubaker, R.R. (1973) J. Bacteriol. 116, 1247–1252.PubMedGoogle Scholar
  3. 3.
    Sancar, A. and Rupp, W.D. (1983) Cell 33, 249–260.PubMedCrossRefGoogle Scholar
  4. 4.
    Thomas, D.C., Levy, M. and Sancar, A. (1985) J. Biol. Chem. 260, 9875–9883.PubMedGoogle Scholar
  5. 5.
    Abdel-Monem, M., Chanal, M.C. and Hoffmann-Berling, H. (1977) Eur. J. Biochem. 79, 33–38.PubMedCrossRefGoogle Scholar
  6. 6.
    Husain, I., Chaney, S.G. and Sancar, A. (1985) J. Bacteriol. 163, 817–823.PubMedGoogle Scholar
  7. 7.
    Beck, D.J., Popoff, S., Sancar, A. and Rupp, W.D. (1985) Nucleic Acids Res 13, 7395–7412.PubMedCrossRefGoogle Scholar
  8. 8.
    Pinto, A.L., Naser, L.J., Essigmann, J.M. and Lippard, S.J. (1986) J. Am. Chem. Soc. 108, 7405–7407.CrossRefGoogle Scholar
  9. 9.
    Popoff, S., Beck, D.J. and Rupp, W.D. (1987) Mutat. Res. 183, 129–137.PubMedGoogle Scholar
  10. 10.
    Husain, I., Van Honten, B., Thomas, D.C., Abdel-Monem, M. and Sancar, A. (1985) Proc. Natl. Acad. Sci. U.S.A 82, 6774–6778.PubMedCrossRefGoogle Scholar
  11. 11.
    Tullius, T.D. and Lippard, S.J. (1981) J. Am. Chem. Soc. 103, 4620–4622.CrossRefGoogle Scholar
  12. 12.
    Royer-Pokora, B., Gordon, L.K., and Haseltine, W.A. (1981) Nucl. Acids Res. 9, 4595–4609.PubMedCrossRefGoogle Scholar
  13. 13.
    Malinge, J.-M., Schwartz, A. and Leng, M. (1987) Nucl. Acids. Res. 15, 1779–1797.PubMedCrossRefGoogle Scholar
  14. 14.
    Pinto, A.L. and Lippard, S.L. (1985) Proc. Natl. Acad. Sci. USA 82, 4616–4619.PubMedCrossRefGoogle Scholar
  15. 15.
    Eastman, A. (1983) Biochemistry 22, 3927–3923.PubMedCrossRefGoogle Scholar
  16. 16.
    Mauldin, S.K., Richard, F.A., Plescia, M., Wyrick, S.D., Sancar, A. and Chaney, S.G. (1986) Anal. Biochem. 157, 129–143.PubMedCrossRefGoogle Scholar
  17. 17.
    Eastman, A. and Bresnick, F. (1981) Biochem. Pharmacol. 30, 2721–2723.PubMedCrossRefGoogle Scholar
  18. 18.
    Villani, G., Lherisson, C., Defais, M. and Johnson, N.P. (1987) Mutat. Res. 183, 21–29.PubMedGoogle Scholar
  19. 19.
    Young, R.C., Van Hoff, D.D., Gormley, P., Makuch, L., Cassidy, J., Howser, D., and Bull, J.M. (1979) Cancer. Treat. Reports 63, 1539–1544.Google Scholar
  20. 20.
    Alberts, D.S., Hilgers, R.D., Moon, T.E., Martinbeau, P.W. and Rivkin, S. (1979) Cancer Treat. Reports, 63, 301–305.Google Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1988

Authors and Affiliations

  • J. D. Page
  • I. Husain
  • S. G. Chaney
  • A. Sancar

There are no affiliations available

Personalised recommendations