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Mutational alteration of the breakage/resealing subunit of bacteriophage T4 DNA topoisomerase confers resistance to antitumor agent m-AMSA.

Publication ,  Journal Article
Huff, AC; Ward, RE; Kreuzer, KN
Published in: Mol Gen Genet
March 1990

Bacteriophage T4 provides a simple model system in which to examine the mechanism of action of antitumor agents that have been proposed to attack type II DNA topoisomerases. Prior results demonstrated that T4 type II DNA topoisomerase is the target of antitumor agent 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) in phage-infected Escherichia coli: a point mutation in topoisomerase structural gene 39 was shown to confer both m-AMSA-resistant phage growth and m-AMSA-insensitive topoisomerase activity. We report here that a point mutation in T4 topoisomerase structural gene 52 can also independently render both phage growth and topoisomerase activity resistant to m-AMSA. The DNA relaxation and DNA cleavage activities of this newly isolated mutant topoisomerase were significantly insensitive to m-AMSA. The drug-resistance mutation in gene 52, as well as that in gene 39, alters the DNA cleavage site specificity of wild-type T4 topoisomerase. This finding is consistent with a mechanism of drug action in which both topoisomerase and DNA participate in formation of the drug-binding site.

Duke Scholars

Published In

Mol Gen Genet

DOI

ISSN

0026-8925

Publication Date

March 1990

Volume

221

Issue

1

Start / End Page

27 / 32

Location

Germany

Related Subject Headings

  • Viral Structural Proteins
  • T-Phages
  • Plant Biology & Botany
  • Phenotype
  • Mutation
  • Genetics & Heredity
  • Genes, Viral
  • Drug Resistance, Microbial
  • DNA, Viral
  • DNA Topoisomerases, Type II
 

Citation

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Huff, A. C., Ward, R. E., & Kreuzer, K. N. (1990). Mutational alteration of the breakage/resealing subunit of bacteriophage T4 DNA topoisomerase confers resistance to antitumor agent m-AMSA. Mol Gen Genet, 221(1), 27–32. https://doi.org/10.1007/BF00280363
Huff, A. C., R. E. Ward, and K. N. Kreuzer. “Mutational alteration of the breakage/resealing subunit of bacteriophage T4 DNA topoisomerase confers resistance to antitumor agent m-AMSA.Mol Gen Genet 221, no. 1 (March 1990): 27–32. https://doi.org/10.1007/BF00280363.
Huff, A. C., et al. “Mutational alteration of the breakage/resealing subunit of bacteriophage T4 DNA topoisomerase confers resistance to antitumor agent m-AMSA.Mol Gen Genet, vol. 221, no. 1, Mar. 1990, pp. 27–32. Pubmed, doi:10.1007/BF00280363.

Published In

Mol Gen Genet

DOI

ISSN

0026-8925

Publication Date

March 1990

Volume

221

Issue

1

Start / End Page

27 / 32

Location

Germany

Related Subject Headings

  • Viral Structural Proteins
  • T-Phages
  • Plant Biology & Botany
  • Phenotype
  • Mutation
  • Genetics & Heredity
  • Genes, Viral
  • Drug Resistance, Microbial
  • DNA, Viral
  • DNA Topoisomerases, Type II