title: Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase.
abstract: 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.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill 27599.
authors.forename: M T
authors.initials: MT
authors.lastname: Howard
authors.forename: S H
authors.initials: SH
authors.lastname: Neece
authors.forename: S W
authors.initials: SW
authors.lastname: Matson
authors.forename: K N
authors.initials: KN
authors.lastname: Kreuzer
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000677:Amsacrine; D017122:Bacteriophage T4 / Q000201:enzymology; D001483:Base Sequence; D004265:DNA Helicases; D004250:DNA Topoisomerases, Type II / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000201:enzymology; D008961:Models, Structural; D008969:Molecular Sequence Data; D010957:Plasmids / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D000677:Amsacrine; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D004250:DNA Topoisomerases, Type II