Dynamics of bleomycin interaction with a strongly bound hairpin DNA substrate, and implications for cleavage of the bound DNA

Trevor C. Bozeman, Rupesh Nanjunda, Chenhong Tang, Yang Liu, Zachary J. Segerman, Paul A. Zaleski, W. David Wilson, Sidney Hecht

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Recent studies involving DNAs bound strongly by bleomycins have documented that such DNAs are degraded by the antitumor antibiotic with characteristics different from those observed when studying the cleavage of randomly chosen DNAs in the presence of excess Fe·BLM. In the present study, surface plasmon resonance has been used to characterize the dynamics of BLM B2 binding to a strongly bound hairpin DNA, to define the effects of Fe 3+, salt, and temperature on BLM-DNA interaction. One strong primary DNA binding site, and at least one much weaker site, were documented. In contrast, more than one strong cleavage site was found, an observation also made for two other hairpin DNAs. Evidence is presented for BLM equilibration between the stronger and weaker binding sites in a way that renders BLM unavailable to other, less strongly bound DNAs. Thus, enhanced binding to a given site does not necessarily result in increased DNA degradation at that site; i.e., for strongly bound DNAs, the facility of DNA cleavage must involve other parameters in addition to the intrinsic rate of C-4′ H atom abstraction from DNA sugars.

Original languageEnglish (US)
Pages (from-to)17842-17845
Number of pages4
JournalJournal of the American Chemical Society
Volume134
Issue number43
DOIs
StatePublished - Oct 31 2012

    Fingerprint

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this