title: Catalytic function of DNA topoisomerase II.
abstract: Although the genetic code is defined by a linear array of nucleotides, it is the three-dimensional structure of the double helix that regulates most of its cellular functions. Over the past two decades, it has become increasingly clear that aspects of this three-dimensionality which reflect topological relationships within the double helix (i.e., superhelical twisting, knotting, or tangling) influence virtually every facet of nucleic acid physiology. In vivo, DNA topology is modulated by ubiquitous enzymes known as topoisomerases. The type II enzyme is essential to the eukaryotic cell and is required for unlinking daughter chromosomes and maintaining chromosome structure. Moreover, topoisomerase II also has been identified as the primary cellular target for several widely used antineoplastic drugs. Before the physiological functions of topoisomerase II can be effectively dissected or its drug interactions fully exploited, it is imperative to understand the mechanism by which this important enzyme carries out its catalytic cycle.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.
authors.forename: N
authors.initials: N
authors.lastname: Osheroff
authors.forename: E L
authors.initials: EL
authors.lastname: Zechiedrich
authors.forename: K C
authors.initials: KC
authors.lastname: Gale
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D002384:Catalysis; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000502:physiology*; D004278:DNA, Superhelical / Q000378:metabolism / Q000648:ultrastructure*; D005057:Eukaryotic Cells / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010766:Phosphorylation; D011485:Protein Binding; D011995:Recombination, Genetic; D013379:Substrate Specificity; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D059005:Topoisomerase II Inhibitors; D000255:Adenosine Triphosphate; D004247:DNA; D004250:DNA Topoisomerases, Type II