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. 1974 Aug;71(8):2973–2977. doi: 10.1073/pnas.71.8.2973

Mechanism of Inhibition of Bacillus subtilis DNA Polymerase III by the Arylhydrazinopyrimidine Antimicrobial Agents

Robert L Low 1,2, Stephan A Rashbaum 1,2, Nicholas R Cozzarelli 1,2
PMCID: PMC388601  PMID: 4213240

Abstract

Arylhydrazinopyrimidines inhibit DNA synthesis in Bacillus subtilis by promoting formation of a specific, long-lived ternary complex with DNA polymerase III and the template-primer DNA. DNA polymerase III contains an associated, single-strand-selective exonuclease which generates 5′-mononucleotides. Drug inhibition of the nuclease similarly proceeds through formation of the ternary complex. The ternary complex was isolated by agarose chromatography. Like inhibition of the nuclease, optimum formation of the complex requires duplex DNA with single-stranded regions such as bacteriophage λ DNA (purely single- and double-stranded DNA are ineffective) and is antagonized by specific deoxyribonucleoside triphosphates. Formation of the ternary complex requires a di- or polyvalent cation and is inhibited by sulfhydryl reagents and high ionic strength. The complex dissociates with a half-life of the order of minutes at 4°.

Keywords: ternary complex, exonuclease, DNA replication, base pairing, polyamine

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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