Novobiocin inhibition of simian virus 40 DNA replication

Research output: Contribution to journalArticle

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Abstract

Supercoiling in eukaryotic cells can be explained by the packaging of DNA into nucleosomes in the presence of nicking-closing enzymes1. This does not, however, rule out the presence of a DNA gyrase. DNA gyrase2 is involved in the introduction and maintenance of supercoiling in prokaryotic cells3-6 and in DNA replication in Escherichia coli4,6,7. Novobiocin and coumermycin-A1 inhibit prokaryotic DNA replication4,7-11 by inhibiting the subunit of the gyrase responsible for its ATPase and energy transduction activities3,4,12-14. The inhibition of DNA synthesis in a mammalian cell15 and in rat liver mitochondria16 by novobiocin suggests that a gyrase required for initiation of replication is inhibited. Because the presence of a gyrase in eukaryotic cells would be of great interest, I have examined this question in a well characterized model system, the replication of simian virus 40 in its host (monkey) cell. The results demonstrate here that novobiocin and coumermycin A1 inhibit SV40 DNA synthesis in mammalian cells and inhibit DNA polymerase α, the replicative DNA polymerase in this system17,18. Novobiocin, but not coumermycin A1, reduces the degree of supercoiling of DNA pulse-labelled in its presence, probably through its inhibition of protein synthesis. Thus the inhibition of SV40 DNA synthesis by novobiocin does not alone prove the involvement of a DNA gyrase.

Original languageEnglish
Pages (from-to)529-531
Number of pages3
JournalNature
Volume286
Issue number5772
DOIs
StatePublished - 1980

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Novobiocin
Simian virus 40
DNA Replication
DNA
DNA Gyrase
Eukaryotic Cells
DNA-Directed DNA Polymerase
DNA Packaging
Escherichia
Nucleosomes
Haplorhini
Adenosine Triphosphatases
Maintenance
Liver
coumermycin

ASJC Scopus subject areas

  • General

Cite this

Novobiocin inhibition of simian virus 40 DNA replication. / Edenberg, Howard.

In: Nature, Vol. 286, No. 5772, 1980, p. 529-531.

Research output: Contribution to journalArticle

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