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Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

DNA Charge Transport Chemistry and Biology

Charge migration through the DNA base stack results in oxidative damage 200 Å from the site of the remotely bound oxidant, but this reaction from a distance is exquisitely sensitive to perturbations in the intervening base stack. We have exploited this DNA charge transport chemistry to develop sensitive electrochemical sensors for perturbations in base stacking as found with DNA mismatches, base lesions as well as protein binding. Additionally, DNA charge transport chemistry may be utilized in carrying out a range of reactions from a distance in DNA: repairing thymine dimers, forming disulfides from nearby thiols, and oxidizing a DNA-bound protein. We have also explored the consequences and opportunities for DNA-mediated charge transport within the cell. Ubiquitous to DNA base excision repair enzymes are 4Fe-4S clusters, and using DNA-based electrochemical sensors, we have found that the redox potentials of the metal clusters shift upon DNA-binding, thus activating the repair proteins for DNA-mediated redox chemistry. We have developed a model for how these redox-activated repair proteins may redistribute onto sites in the genome near damage using DNA charge transport chemistry. Biochemical and genetic experiments have been used to test this model. These data support the idea that DNA charge transport chemistry may be used advantageously in the cell in the search for DNA base damage.

Acknowledgments

We are grateful to the NIH (GM61077 and GM49216) for financial support.

References
  1. Delaney and Barton. JOC 68, 6475-6483 (2003).
  2. Drummond, Hill, and Barton. Nature Biotechnology 21, 1192-1199 (2003).
  3. Boal et al. Biochemistry 44, 8397-8407 (2005).
  4. Takada and Barton. JACS 127, 12204-12205 (2005).
  5. Yavin et al. PNAS 102, 3546-3551 (2005).
  6. Yavin et al. PNAS 103, 3610-3614 (2006).
  7. Gorodetsky, Boal, and Barton. JACS 128, 12082-12083 (2006).

Jacqueline K. Barton

Division of Chemistry and Chemical Engineering
California Institute of Technology
Pasadena, CA 91125

Phone 626-395-3200
Fax: 626-577-4976
Email: jkbarton@caltech.edu