Title: "Signaling through DNA"

Jacqueline K. Barton
John G. Kirkwood and Arthur A. Noyes Professor, Emerita
California Institute of Technology, Pasadena, CA 91125

My laboratory has focused on understanding electron transfer chemistry through DNA. Double helical DNA provides a medium for efficient redox chemistry over very long molecular distances. But we have learned that this redox chemistry depends sensitively upon DNA base pair stacking; any perturbation in DNA stacking, such as occurs with base mismatches, lesions, and protein binding, turns off the efficient electron transfer chemistry through the base pair stack. Thus this DNA charge transport chemistry depends sensitively upon the integrity of the DNA duplex. We have also been exploring how this chemistry may be used within the cell. Increasingly, iron-sulfur clusters are being found in DNA-binding proteins involved in genome maintenance. These metal clusters, common redox cofactors, are associated not only with DNA repair proteins but also proteins involved in DNA replication, including our DNA polymerases. We have found that the metal clusters in these DNA-binding proteins are redox-active. Moreover this chemistry leads to a redox switch to control DNA binding. This redox chemistry at a distance, mediated by the DNA helix, thus offers a route for long range signaling and coordination of DNA-processing proteins across the genome.