Damage to DNA by long-range charge transport
Photochemical reactions on DNA assemblies containing tethered photooxidants, particularly metallointercalating photooxidants, have been critical in establishing that permanent damage to DNA bases can be generated as a result of radical migration from a remote site on the DNA duplex. Induction of a 1-electron deficiency in the oxidant attached covalently to the DNA remote from the oxidizable site leads to this "chemistry at a distance," caused by efficient charge transport through the DNA base pair stack. Double helical DNA may be unique as a polymeric assembly in solution because of this interior core of stacked aromatic heterocyclic base pairs. Similarly stacked solid-state materials tend to be conducting along the stacking direction. This chapter describes the design and construction of DNA assemblies used to probe long-range oxidative damage in DNA. It also includes methodology for the oxidative repair of a thymine dimer lesion in DNA, as this "chemistry at a distance" also depends on long-range charge transfer through the DNA base pair stack.
© 2000 Academic Press. We are grateful to the NIH (GM49216) for their financial support of this research. We also thank the American Cancer Society for a postdoctoral fellowship (to S.R.R.) and the Howard Hughes Medical Institute for a predoctoral fellowship (to M.E.N.). Most of all we thank the many talented scientists whose work contributed to that described here, especially Drs. D. B. Hall, M. R. Arkin, R. E. Holmlin, and P. J. Dandliker.