Inhibition of RNA and DNA polymerases by the product of the reaction of selenite with sulfhydryl compounds

GD Frenkel, A Walcott and C Middleton

Sodium selenite has previously been shown to inhibit DNA and RNA synthesis in both intact cells and isolated nuclei. Nevertheless, DNA and RNA polymerases, the enzymes responsible for this synthesis, are insensitive to inhibition by selenite. Several DNA and RNA polymerases have now been shown to be inhibited by selenite in the presence of sulfhydryl compounds. This inhibition is due to the reaction of selenite with the sulfhydryl compounds to form selenotrisulfide derivatives which inhibit the enzymes. The selenotrisulfides decrease the Vmax of the polymerase reaction and increase the apparent Km for the triphosphates, but do not alter the apparent Km of the enzyme for the DNA template. There are differences in potency between selenotrisulfides formed from similar sulfhydryl compounds such as mercaptoethanol and mercaptoethylamine. There are also differences in the sensitivity of different polymerases to inhibition by the selenotrisulfides.

Volume 31, Issue 1, pp. 112-116, 01/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

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