DNA-mediated charge transport for DNA repair

Elizabeth M. Boon, Alison L. Livingston, Nikolas H. Chmiel, Sheila S. David, Jacqueline K. Barton

Research output: Contribution to journalArticle

187 Scopus citations

Abstract

MutY, like many DNA base excision repair enzymes, contains a [4Fe4S] 2+ cluster of undetermined function. Electrochemical studies of MutY bound to a DNA-modified gold electrode demonstrate that the [4Fe4S] cluster of MutY can be accessed in a DNA-mediated redox reaction. Although not detectable without DNA, the redox potential of DNA-bound MutY is ≈275 mV versus NHE, which is characteristic of HiPiP iron proteins. Binding to DNA is thus associated with a change in [4Fe4S]3+/2+ potential, activating the cluster toward oxidation. Given that DNA charge transport chemistry is exquisitely sensitive to perturbations in base pair structure, such as mismatches, we propose that this redox process of MutY bound to DNA exploits DNA charge transport and provides a DNA signaling mechanism to scan for mismatches and lesions in vivo.

Original languageEnglish (US)
Pages (from-to)12543-12547
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number22
DOIs
StatePublished - Oct 28 2003
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

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    Boon, E. M., Livingston, A. L., Chmiel, N. H., David, S. S., & Barton, J. K. (2003). DNA-mediated charge transport for DNA repair. Proceedings of the National Academy of Sciences of the United States of America, 100(22), 12543-12547. https://doi.org/10.1073/pnas.2035257100