Redox signaling between DNA repair proteins for efficient lesion detection
Name
Boal-2009-Redox signaling betw.pdf
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1.07 MB
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Author(s)
Barton, Jacqueline K.
Gralnick, Jeffrey A.
Sontz, Pamela A.
Genereux, Joseph C.
Boal, Amie K.
Newman, Dianne K
Date Issued
August 2009
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
United States National Academy of Sciences
Citation
Boal, 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 Sciences
Version
Final published version
Abstract
Base 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences
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Article 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.
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DOI of Published Version
http://dx.doi.org/10.1073/pnas.0908059106
