DNA-mediated signaling among proteins with [4Fe4S] clusters

Abstract

Double helical DNA can serve as a conduit for efficient redox chem. over long mol. distances. We have now been exploring how this chem. may be used within the cell for long range signaling. Increasingly, [4Fe4S] clusters are being found in DNA-binding proteins involved in genome maintenance. These [4Fe4S] 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 this chem. is important in the context of oxidative damage and may provide a first step in how DNA repair proteins may localize in the vicinity of lesions. Moreover, DNA-mediated signaling among clusters may serve to coordinate the proteins involved in replication. This redox chem. at a distance, mediated by the DNA helix, thus offers a route for long range signaling among DNA-processing proteins across the genome.