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dc.contributor.authorNewman, Dianne K.
dc.contributor.authorBarton, Jacqueline K.
dc.contributor.authorGralnick, Jeffrey A.
dc.contributor.authorSontz, Pamela A.
dc.contributor.authorGenereux, Joseph C.
dc.contributor.authorBoal, Amie K.
dc.date.accessioned2010-05-05T16:59:30Z
dc.date.available2010-05-05T16:59:30Z
dc.date.issued2009-08
dc.date.submitted2009-07
dc.identifier.issn1091-6490
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/1721.1/54715
dc.description.abstractBase excision repair (BER) enzymes maintain the integrity of the genome, and in humans, BER mutations are associated with cancer. Given the remarkable sensitivity of DNA-mediated charge transport (CT) to mismatched and damaged base pairs, we have proposed that DNA repair glycosylases (EndoIII and MutY) containing a redox-active [4Fe4S] cluster could use DNA CT in signaling one another to search cooperatively for damage in the genome. Here, we examine this model, where we estimate that electron transfers over a few hundred base pairs are sufficient for rapid interrogation of the full genome. Using atomic force microscopy, we found a redistribution of repair proteins onto DNA strands containing a single base mismatch, consistent with our model for CT scanning. We also demonstrated in Escherichia coli a cooperativity between EndoIII and MutY that is predicted by the CT scanning model. This relationship does not require the enzymatic activity of the glycosylase. Y82A EndoIII, a mutation that renders the protein deficient in DNA-mediated CT, however, inhibits cooperativity between MutY and EndoIII. These results illustrate how repair proteins might efficiently locate DNA lesions and point to a biological role for DNA-mediated CT within the cell.en
dc.language.isoen_US
dc.publisherUnited States National Academy of Sciencesen
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.0908059106en
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en
dc.sourcePNASen
dc.titleRedox signaling between DNA repair proteins for efficient lesion detectionen
dc.typeArticleen
dc.identifier.citationBoal, Amie K et al. “Redox signaling between DNA repair proteins for efficient lesion detection.” Proceedings of the National Academy of Sciences 106.36 (2009): 15237-15242. © 2009 National Academy of Sciencesen
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciencesen_US
dc.contributor.approverNewman, Dianne K.
dc.contributor.mitauthorNewman, Dianne K.
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen
dc.eprint.versionFinal published versionen
dc.type.urihttp://purl.org/eprint/type/JournalArticleen
eprint.statushttp://purl.org/eprint/status/PeerRevieweden
dspace.orderedauthorsBoal, A. K.; Genereux, J. C.; Sontz, P. A.; Gralnick, J. A.; Newman, D. K.; Barton, J. K.en
mit.licensePUBLISHER_POLICYen


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