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

Eylon Yavin, Eric D A Stemp, Valerie L. O'Shea, Sheila S. David, Jacqueline K. Barton

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

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 π-stack, and trapping efficiency is increased when a non-cleavable 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.

Original languageEnglish (US)
Pages (from-to)3610-3614
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number10
DOIs
StatePublished - Mar 7 2006
Externally publishedYes

Keywords

  • Base excision repair
  • DNA charge transport
  • Iron sulfur clusters

ASJC Scopus subject areas

  • Genetics
  • General

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