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Electron trap for DNA-bound repair enzymes: A strategy for DNA-mediated signaling

Yavin, Eylon and Stemp, Eric D. A. and O'Shea, Valerie L. and David, Sheila S. and Barton, Jacqueline K. (2006) Electron trap for DNA-bound repair enzymes: A strategy for DNA-mediated signaling. Proceedings of the National Academy of Sciences of the United States of America, 103 (10). pp. 3610-3614. ISSN 0027-8424. PMCID PMC1450131.

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Despite a low copy number within the cell, base excision repair (BER) enzymes readily detect DNA base lesions and mismatches. These enzymes also contain [Fe4S4] clusters, yet a redox role for these iron cofactors had been unclear. Here, we provide evidence that BER proteins may use DNA-mediated redox chemistry as part of a signaling mechanism to detect base lesions. By using chemically modified bases, we show electron trapping on DNA in solution with bound BER enzymes by electron paramagnetic resonance (EPR) spectroscopy. We demonstrate electron transfer from two BER proteins, Endonuclease III (EndoIII) and MutY, to modified bases in DNA containing oxidized nitroxyl radical EPR probes. Electron trapping requires that the modified base is coupled to the DNA {pi}-stack, and trapping efficiency is increased when a noncleavable MutY substrate analogue is located distally to the trap. These results are consistent with DNA binding leading to the activation of the repair proteins toward oxidation. Significantly, these results support a mechanism for DNA repair that involves DNA-mediated charge transport.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Stemp, Eric D. A.0000-0003-2098-4214
David, Sheila S.0000-0001-5873-7935
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2006 by The National Academy of Sciences of the USA Contributed by Jacqueline K. Barton, January 10, 2006. Published online before print February 27, 2006, 10.1073/pnas.0600239103 We thank A. Boal for preparation of EndoIII and E. Khamou for technical assistance. This work was supported by National Institutes of Health Grants GM49216 (to J.K.B.) and CA67985 (to S.S.D.). Author contributions: E.Y., E.D.A.S., S.S.D., and J.K.B. designed research; E.Y. performed research; V.L.O. and S.S.D. contributed new reagents/analytic tools; E.Y. and J.K.B. analyzed data; and E.Y., S.S.D., and J.K.B. wrote the paper. Conflict of interest statement: No conflicts declared.
Funding AgencyGrant Number
Subject Keywords:base excision repair; DNA charge transport; iron sulfur clusters
Issue or Number:10
PubMed Central ID:PMC1450131
Record Number:CaltechAUTHORS:YAVpnas06
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Official Citation:Eylon Yavin, Eric D. A. Stemp, Valerie L. O’Shea, Sheila S. David, and Jacqueline K. Barton Electron trap for DNA-bound repair enzymes: A strategy for DNA-mediated signaling PNAS 2006 103 (10) 3610-3614; published ahead of print February 27, 2006, doi:10.1073/pnas.0600239103
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5068
Deposited By: Archive Administrator
Deposited On:26 Sep 2006
Last Modified:02 Mar 2023 22:26

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