Uranyl acetate as a direct inhibitor of DNA-binding proteins

Wendy J. Hartsock, Jennifer D. Cohen, David Segal

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Zinc finger proteins, one of the largest families of DNA-binding proteins in higher eukaryotes, are so named because they require zinc ions for appropriate structure and function. Dysregulation of zinc finger-containing DNA transcription and repair proteins has been proposed as a potential mechanism for the toxic effects of some metal ions. Uranium metal has been reported to be both a cytotoxic and a genotoxic agent. We hypothesized that these toxic effects of uranium might be due to its ability to directly disrupt zinc finger activity. To test this hypothesis, two purified zinc finger proteins, Aart and Sp1, were analyzed by electrophoretic mobility shift in the presence of uranyl acetate. Inhibition of binding was apparent at 10 μM uranyl acetate, while no inhibition was observed with up to 2000 μM the cytotoxic metalloid sodium arsenite. Preincubation of the DNA with uranyl acetate did not inhibit zinc finger protein binding, suggesting that the inhibition was due to direct uranyl interaction with the protein. Surprisingly, uranyl acetate inhibited two nonzinc finger DNA-binding proteins, AP1 and NF-κB, to a similar extent, and zinc finger inhibition was reduced in the presence of bovine serum albumin. These results suggest that uranium can directly inhibit the function of DNA-binding proteins, most likely via a nonspecific protein interaction.

Original languageEnglish (US)
Pages (from-to)784-789
Number of pages6
JournalChemical Research in Toxicology
Volume20
Issue number5
DOIs
StatePublished - May 2007

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Uranyl acetate as a direct inhibitor of DNA-binding proteins'. Together they form a unique fingerprint.

  • Cite this