DNA-mediated Charge Transport for

DNA Repair

Posted: October 21, 2005

DNA-mediated charge transport for DNA repair

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

*Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125; and Department of Chemistry, University of Utah, Salt Lake City, UT 84112

Contributed by Jacqueline K. Barton, August 15, 2003

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.

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Abbreviations: Endo III, endonuclease III; CT, charge transport; MBP, maltose-binding protein; CV, cyclic voltammetry.
To whom correspondence should be addressed. E-mail: jkbarton@caltech.edu or david@chem.utah.edu."