KCS

Many experiments have now shown that double helical DNA may serve as a conduit for efficient redox chemistry over long molecular distances. This chemistry is exquisitely sensitive to perturbations in the DNA base stack, such as arise with base mismatches, lesions, and protein binding. We have explored how this chemistry may be used within the cell for long range signaling. Increasingly, 4Fe-4S clusters are being found in DNA-binding proteins involved in genome maintenance. These 4Fe-4S clusters, common redox cofactors, are associated not only with repair proteins but also DNA polymerases and primase. Studies are described to characterize DNA–mediated charge transport by these metalloproteins. Experiments indicate that this chemistry is important in the context of oxidative damage and also may provide a first step in how DNA repair proteins may localize in the vicinity of lesions. This redox chemistry at a distance, mediated by the DNA helix, offers a route for long range signaling among DNA-processing proteins across the genome.