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Bacteriophage T4 mutants hypersensitive to an antitumor agent that induces topoisomerase-DNA cleavage complexes.

Publication ,  Journal Article
Woodworth, DL; Kreuzer, KN
Published in: Genetics
July 1996

Many antitumor agents and antibiotics affect cells by interacting with type II topoisomerases, stabilizing a covalent enzyme-DNA complex. A pathway of recombination can apparently repair this DNA damage. In this study, transposon mutagenesis was used to identify possible components of the repair pathway in bacteriophage T4. Substantial increases in sensitivity to the antitumor agent m-AMSA [4'-(9-acridinylamino)methanesulfon-m-anisidide] were found with transposon insertion mutations that inactivate any of six T4-encoded proteins: UvsY (DNA synaptase accessory protein), UvsW (unknown function), Rnh (RNase H and 5' to 3' DNA exonuclease), alpha-gt (alpha-glucosyl transferase), gp47.1 (uncharacterized), and NrdB (beta subunit of ribonucleotide reductase). The role of the rnh gene in drug sensitivity was further characterized. First, an in-frame rnh deletion mutation was constructed and analyzed, providing evidence that the absence of Rnh protein causes hypersensitivity to m-AMSA. Second, the m-AMSA sensitivity of the rnh-deletion mutant was shown to require a drug-sensitive T4 topoisomerase. Third, analysis of double mutants suggested that uvsW and rnh mutations impair a common step in the recombinational repair pathway for m-AMSA-induced damage. Finally, the rnh-deletion mutant was found to be hypersensitive to UV, implicating Rnh in recombinational repair of UV-induced damage.

Duke Scholars

Published In

Genetics

DOI

ISSN

0016-6731

Publication Date

July 1996

Volume

143

Issue

3

Start / End Page

1081 / 1090

Location

United States

Related Subject Headings

  • Viral Proteins
  • Ultraviolet Rays
  • Ribonuclease H
  • Mutagenesis, Insertional
  • Molecular Sequence Data
  • Membrane Proteins
  • Exodeoxyribonucleases
  • Exodeoxyribonuclease V
  • Developmental Biology
  • DNA-Binding Proteins
 

Citation

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Woodworth, D. L., & Kreuzer, K. N. (1996). Bacteriophage T4 mutants hypersensitive to an antitumor agent that induces topoisomerase-DNA cleavage complexes. Genetics, 143(3), 1081–1090. https://doi.org/10.1093/genetics/143.3.1081
Woodworth, D. L., and K. N. Kreuzer. “Bacteriophage T4 mutants hypersensitive to an antitumor agent that induces topoisomerase-DNA cleavage complexes.Genetics 143, no. 3 (July 1996): 1081–90. https://doi.org/10.1093/genetics/143.3.1081.
Woodworth, D. L., and K. N. Kreuzer. “Bacteriophage T4 mutants hypersensitive to an antitumor agent that induces topoisomerase-DNA cleavage complexes.Genetics, vol. 143, no. 3, July 1996, pp. 1081–90. Pubmed, doi:10.1093/genetics/143.3.1081.

Published In

Genetics

DOI

ISSN

0016-6731

Publication Date

July 1996

Volume

143

Issue

3

Start / End Page

1081 / 1090

Location

United States

Related Subject Headings

  • Viral Proteins
  • Ultraviolet Rays
  • Ribonuclease H
  • Mutagenesis, Insertional
  • Molecular Sequence Data
  • Membrane Proteins
  • Exodeoxyribonucleases
  • Exodeoxyribonuclease V
  • Developmental Biology
  • DNA-Binding Proteins