DNA Protection by the Bacterial Ferritin Dps via DNA Charge Transport

Abstract

Dps proteins, bacterial mini-ferritins that protect DNA from oxidative stress, are implicated in the survival and virulence of pathogenic bacteria. Here we examine the mechanism of E. coli Dps protection of DNA, specifically whether this DNA-binding protein can utilize DNA charge transport through the base pair π-stack to protect the genome from a distance. An intercalating ruthenium photooxidant was employed to generate DNA damage localized to guanine repeats, the sites of lowest potential in DNA. We find that Dps loaded with ferrous iron, in contrast to Apo-Dps and ferric iron-loaded Dps, significantly attenuates the yield of oxidative DNA damage. These data demonstrate that ferrous iron-loaded Dps is selectively oxidized to fill guanine radical holes, thereby restoring the integrity of the DNA. Luminescence studies indicate no direct interaction between the ruthenium photooxidant and Dps, supporting the DNA-mediated oxidation of ferrous iron-loaded Dps. Thus DNA charge transport may be a mechanism by which Dps efficiently protects the genome of pathogenic bacteria from a distance.