PMID: 9419336Feb 21, 1998Paper

Supercoiling affects the accessibility of glutathione to DNA-bound molecules: positive supercoiling inhibits calicheamicin-induced DNA damage

Proceedings of the National Academy of Sciences of the United States of America
W A LaMarrP C Dedon

Abstract

DNA superhelical tension, an important feature of genomic organization, is known to affect the interactions of intercalating molecules with DNA. However, the effect of torsional tension on nonintercalative DNA-binding chemicals has received less attention. We demonstrate here that the enediyne calicheamicin gamma1I, a strand-breaking agent specific to the minor groove, causes approximately 50% more damage in negatively supercoiled plasmid DNA than in DNA with positive superhelicity. Furthermore, we show that the decrease in damage in positively supercoiled DNA is controlled at the level of thiol activation of the drug. Our results suggest that supercoiling may affect both the activity of nonintercalating genotoxins in vivo and the accessibility of glutathione and other small physiologic molecules to DNA-bound chemicals or reactions occurring in the grooves of DNA.

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Citations

Mar 7, 2002·Chemistry & Biology·Coran M H WatanabePeter G Schultz
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May 28, 2019·Genes & Development·Belén Gómez-González, Andrés Aguilera
Jul 31, 2019·Nature Structural & Molecular Biology·Matthew WootenXin Chen
Dec 7, 2007·Chemical Research in Toxicology·Peter C Dedon
May 6, 2019·Journal of the American Chemical Society·Hao ZhangK C Nicolaou

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