Boon, Elizabeth M. and Livingston, Alison L. and Chmiel, Nikolas H. and David, Sheila S. and Barton, Jacqueline K. (2003) DNA-mediated charge transport for DNA repair. Proceedings of the National Academy of Sciences of the United States of America, 100 (22). pp. 12543-12547. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:BOOpnas03
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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 approximate to275 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.
|Additional Information:||© 2003 by the National Academy of Sciences. Contributed by Jacqueline K. Barton, August 15, 2003. Published online before print October 14, 2003. We thank D. Ceres for technical assistance, M.-P. Golinelli for preparation of MutY mutants, and M. G. Hill and E. D. A. Stemp for helpful discussions. We thank the National Institutes of Health and the National Foundation for Cancer Research for their financial support of this research.|
|Subject Keywords:||ESCHERICHIA-COLI MUTY, IRON-SULFUR CLUSTER, ADENINE GLYCOSYLASE MUTY, SITE-DIRECTED MUTAGENESIS, MODIFIED GOLD ELECTRODES, C-TERMINAL DOMAIN, G-A MISPAIRS, ENDONUCLEASE-III, DIRECT ELECTROCHEMISTRY, <4FE-4S>(2+) CLUSTER|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||08 Sep 2005|
|Last Modified:||26 Dec 2012 08:40|
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