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Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase.

Publication ,  Journal Article
Howard, MT; Neece, SH; Matson, SW; Kreuzer, KN
Published in: Proc Natl Acad Sci U S A
December 6, 1994
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The type II DNA topoisomerases are targets for a variety of chemotherapeutic agents, including the antibacterial quinolones and several families of antitumor drugs. These agents stabilize an enzyme-DNA cleavage complex that consists of the topoisomerase covalently linked to the 5' phosphates of a double-stranded DNA break. Although the drug-stabilized cleavage complex is readily reversible, it can result in cell death by a mechanism that remains uncertain. Here we demonstrate that the action of a DNA helicase can convert the cleavage complex into a nonreversible DNA break by displacing DNA strands from the complex. Formation of a nonreversible DNA break, induced by a DNA helicase, could explain the cytotoxicity of these topoisomerase poisons.

Duke Scholars

Kenneth N. Kreuzer
Author Kenneth N. Kreuzer Biochemistry
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Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.91.25.12031

ISSN

0027-8424

Publication Date

December 6, 1994

Volume

91

Issue

25

Start / End Page

12031 / 12035

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Protein Binding
  • Plasmids
  • Molecular Sequence Data
  • Models, Structural
  • Escherichia coli
  • Electrophoresis, Polyacrylamide Gel
  • DNA Topoisomerases, Type II
  • DNA Helicases
  • Base Sequence
 

Citation

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Howard, M. T., Neece, S. H., Matson, S. W., & Kreuzer, K. N. (1994). Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase. Proc Natl Acad Sci U S A, 91(25), 12031–12035. https://doi.org/10.1073/pnas.91.25.12031
Howard, M. T., S. H. Neece, S. W. Matson, and K. N. Kreuzer. “Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase.” Proc Natl Acad Sci U S A 91, no. 25 (December 6, 1994): 12031–35. https://doi.org/10.1073/pnas.91.25.12031.
Howard MT, Neece SH, Matson SW, Kreuzer KN. Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12031–5.
Howard, M. T., et al. “Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase.” Proc Natl Acad Sci U S A, vol. 91, no. 25, Dec. 1994, pp. 12031–35. Pubmed, doi:10.1073/pnas.91.25.12031.
Howard MT, Neece SH, Matson SW, Kreuzer KN. Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12031–12035.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.91.25.12031

ISSN

0027-8424

Publication Date

December 6, 1994

Volume

91

Issue

25

Start / End Page

12031 / 12035

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Protein Binding
  • Plasmids
  • Molecular Sequence Data
  • Models, Structural
  • Escherichia coli
  • Electrophoresis, Polyacrylamide Gel
  • DNA Topoisomerases, Type II
  • DNA Helicases
  • Base Sequence