Evidence for DNA charge transport in the nucleus

Oxidative damage to DNA bases in isolated HeLa nuclei occurs upon treatment with rhodium intercalators and photoactivation. Oxidation occurs preferent ially at the 5'-guanine of 5'-GG-3' sites, indicative of base damage by DNA -mediated charge transfer chemistry. Moreover, oxidative damage occurs at p rotein-bound sites which are inaccessible to rhodium. Thus, on transcriptio nally active DNA within the cell nucleus, DNA-mediated charge transport lea ds to base damage from a distance, and direct interaction of an oxidant is not necessary to generate a base lesion at a specific site. These observati ons require consideration in designing new chemotherapeutics and in underst anding cellular mechanisms for DNA damage and repair.