title: High affinity interaction of mammalian DNA topoisomerase I with short single- and double-stranded oligonucleotides.
abstract: The interaction of DNA topoisomerase I (topo I) with a set of single- and double-stranded oligonucleotides containing 5-27 mononucleotides was investigated. All single- and double-stranded oligonucleotides were found to inhibit competitively the supercoiled DNA relaxation reaction catalyzed by topo I. The enzyme affinity for specific sequence pentanucleotides of the scissile (GACTT, Ki = 2 microM) and non-cleaved chain (AAGTC, Ki = 110 microM) is about 2-4 orders of magnitude higher than that for non-specific oligonucleotides. This specific sequence affinity increases in several cases; lengthening of single-stranded oligonucleotides, formation of stable duplexes between complementary oligonucleotides and preincubation of the enzyme with ligands before addition of supercoiled DNA. We assume that oligonucleotides having a high affinity to the enzyme can offer a unique opportunity for rational design of topoisomerase-targeting drugs.
authors.affiliation: Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of the Russian Academy of Sciences.
authors.forename: G A
authors.initials: GA
authors.lastname: Nevinsky
authors.forename: D V
authors.initials: DV
authors.lastname: Bugreev
authors.forename: V N
authors.initials: VN
authors.lastname: Buneva
authors.forename: Y
authors.initials: Y
authors.lastname: Yasui
authors.forename: M
authors.initials: M
authors.lastname: Nishizawa
authors.forename: T
authors.initials: T
authors.lastname: Andoh
mesh_terms: D001483:Base Sequence; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; D004278:DNA, Superhelical; D009841:Oligonucleotides; D004264:DNA Topoisomerases, Type I