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 preferentially at the 5'-guanine of 5'-GG-3' sites, indicative of base damage by DNA-mediated charge transfer chemistry. Moreover, oxidative damage occurs at protein-bound sites which are inaccessible to rhodium. Thus, on transcriptionally active DNA within the cell nucleus, DNA-mediated charge transport leads 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 observations require consideration in designing new chemotherapeutics and in understanding cellular mechanisms for DNA damage and repair.
© 2001 American Chemical Society. Received July 26, 2001. Publication Date (Web): September 27, 2001. We thank Ning Ye, Shu-mei Dai, and Steven Bates for their technical assistance, Timothy O'Connor for the Fapy/EndoIII enzyme mixture, and Daniel Hall and Katherine Noyes for their help with the synthesis of Rh(phi)_2DMB^(3+). This work was supported by a grant from the NIH (GM49216) as well as funding from the National Foundation for Cancer Research and the Howard Hughes Medical Institute predoctoral fellowship program (M.E.N.).