DNA-mediated signaling

Abstract

Many expts. have now shown that double helical DNA can serve as a conduit for efficient charge transport over long mol. distances. This chem. is exquisitely sensitive to perturbations in the DNA base stack, such as arise with base mismatches, lesions, and protein binding. We have now been exploring how this chem. 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 assocd. not only with repair proteins but also DNA polymerases and primase. Studies are described to characterize DNA-mediated charge transport by these metalloproteins. Expts. indicate that long range DNA charge transport can provide a first step in how DNA repair proteins may localize in the vicinity of lesions. DNA charge transport, in carrying out redox chem. at a distance, offers a route for long range signaling and coordination of DNA repair and DNA-processing proteins across the genome.