title: 2',5'-oligoadenylates inhibit relaxation of supercoiled DNA by calf thymus DNA topoisomerase I.
abstract: DNA topoisomerases interconvert various topological isomers of DNA and play key roles in replication and gene expression. The possible involvement of the 2',5'-oligoadenylates (2-5A) system in cell growth, regulation, and cell differentiation led us to investigate the effects of 2-5A on mammalian topoisomerases. We found that the calf thymus type I topoisomerase was inhibited by a variety of 2-5A compounds. The level of inhibition was dependent upon the number of residues and the degree of phosphorylation at the 5' terminus. The 5'-triphosphorylated 2',5' hexamer, ppp(Ap)5A, was the most effective, strongly reducing relaxation at less than micromolar concentrations. These results raise the possibility that physiological concentrations of 2-5A of sufficient chain length may be capable of regulating gene expression by virtue of a direct inhibition of DNA topoisomerase I.
authors.affiliation: Department of Biochemistry, Eastern Virginia Medical School, Norfolk 23501.
authors.forename: F J
authors.initials: FJ
authors.lastname: Castora
authors.forename: C E
authors.initials: CE
authors.lastname: Erickson
authors.forename: T
authors.initials: T
authors.lastname: Kovács
authors.forename: K
authors.initials: K
authors.lastname: Lesiak
authors.forename: P F
authors.initials: PF
authors.lastname: Torrence
mesh_terms: D000227:Adenine Nucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D004278:DNA, Superhelical / Q000187:drug effects*; D004587:Electrophoresis, Agar Gel; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D009841:Oligonucleotides / Q000494:pharmacology; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D010766:Phosphorylation; D013950:Thymus Gland / Q000201:enzymology*; D059004:Topoisomerase I Inhibitors
chemical_list: D000227:Adenine Nucleotides; D000998:Antiviral Agents; D004278:DNA, Superhelical; D009841:Oligonucleotides; D009843:Oligoribonucleotides; D059004:Topoisomerase I Inhibitors; C023505:2',5'-oligoadenylate