Book of Abstracts: Albany 2003
June 17-21 2003
Oxidative Damage by DNA-Mediated Charge Transport
The base pair stack within B-DNA serves as an efficient medium for charge transport (CT). As a result, oxidative damage to DNA can be generated from an oxidant bound at a remote site. We have utilized tethered metallointercalators as photoactivated oxidants to probe DNA CT and long range oxidative damage. Ruthenium complexes of dipyridophenazine provide spectroscopic probes; with these tethered assemblies, we have monitored DNA CT to form product radicals over 30 Å from the site of ruthenium intercalation at rates ≥ 107 s-1. By varying the intervening DNA sequence, including sequences lacking guanines, we have explored DNA CT mechanistically. Sequence-dependant structure and dynamics modulate CT and also control hole localization versus propagation. Rhodium metallointercalators, as potent photooxidants, also provide useful probes of DNA CT. Utilizing phenanthrenequinone diimine complexes of rhodium, we have probed DNA CT in telomeric sequences, in nucleosomes, and in vivo. Studies of long range oxidative damage with these metallointercalators allow us to test the physiological consequences and opportunities for DNA CT.
California Institute of Technology