DNA-mediated charge transport: From metal complexes to metalloproteins

Abstract

Double helical DNA can serve as a conduit for efficient charge transport (CT) over long mol. distances. Expts. to probe this chem. began more than twenty years ago by examg. electron transfer between simple metal complexes bound to DNA. Over the past several years, [4Fe4S] clusters have been found in DNA-binding proteins involved in genome maintenance and we have turned to asking whether the metal cofactors might utilize this long range CT chem. within the cell. The [4Fe4S] clusters, common redox cofactors, are assocd. not only with DNA repair proteins but also with DNA polymerases, indeed a host of proteins involved in DNA processing. Studies are described to characterize DNA-mediated charge transport by these DNA-binding metalloproteins. Expts. indicate that DNA CT chem. may provide a first step in how DNA repair proteins may localize in the vicinity of lesions. Moreover, DNA-mediated signaling among [4Fe4S] clusters may serve to coordinate the proteins involved in replication. This redox chem. mediated by the DNA helix provides a route for long range signaling among DNA-processing proteins contg. metallo-cofactors across the genome.