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pubmed:abstractText |
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.
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