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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Howard, MT; Neece, SH; Matson, SW; Kreuzer, KN

Published Date

  • December 6, 1994

Published In

Volume / Issue

  • 91 / 25

Start / End Page

  • 12031 - 12035

PubMed ID

  • 7991579

Pubmed Central ID

  • 7991579

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.91.25.12031

Language

  • eng

Conference Location

  • United States