Inhibition of eukaryotic topoisomerase II by ultraviolet-induced cyclobutane pyrimidine dimers

A. H. Corbett, E. L. Zechiedrich, R. S. Lloyd, N. Osheroff

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The effects of short wave ultraviolet (UV)-induced DNA lesions on the catalytic activity of Drosophila melanogaster topoisomerase II were investigated. The presence of these photoproducts impaired the enzyme's ability to relax negatively supercoiled pBR322 plasmid molecules. As determined by DNA photolyase-catalyzed photoreactivation experiments, enzyme inhibition was due to the presence of cyclobutane pyrimidine dimers in the DNA. When 10-20 cyclobutane dimers were present per plasmid, the initial velocity of topoisomerase II-catalyzed DNA relaxation was inhibited ~50%. Decreased relaxation activity correlated with an inhibition of the DNA strand passage step of the enzyme's catalytic cycle. In contrast, UV-induced photoproducts did not alter the prestrand passage DNA cleavage/religation equilibrium of topoisomerase II either in the absence or presence of antineoplastic agents. Results of the present study demonstrate that the repair of cyclobutane pyrimidine dimers is important for the efficient catalytic function of topoisomerase II.

Original languageEnglish (US)
Pages (from-to)19666-19671
Number of pages6
JournalJournal of Biological Chemistry
Volume266
Issue number29
StatePublished - Jan 1 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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