Two Actions of Bleomycin on Superhelical DNA

Steven L. Ross, Robb E. Moses

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Bleomycin is an antitumor and antimicrobial drug which appears to exert a direct effect on DN A in vivo. A shift to lower molecular weight as defined by alkaline isokinetic analysis after exposure to bleomycin has been interpreted as indicating that the drug causes single-strand nicks in the DNA. We have used ØX174 RF1 DNA as a substrate for bleomycin since a single nick in the supercoil produces a marked change in sedimentation properties. We find that bleomycin-treated ØX174 DNA sediments through alkaline sucrose in a manner indicating strand breakage. However, we do not observe any change between bleomycin-treated and untreated DNA when sedimentation is done on neutral gradients. This result indicates that bleomycin induces alkaline-sensitive sites in the DNA but does not cause a single-strand break. The alkaline sensitivity of bleomycin-treated DNA is not increased by heating, a different result than with alkylation of DNA. Phosphodiester bond cleavage does occur in neutral conditions if dithiothreitol is added to the incubation mixture. Our results are compatible with Femoval of a base moiety by bleomycin and with strand scission when dithiothreitol is present.

Original languageEnglish (US)
Pages (from-to)581-586
Number of pages6
JournalBiochemistry
Volume17
Issue number4
DOIs
StatePublished - 1978

ASJC Scopus subject areas

  • Biochemistry

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