Long-range oxidative damage to DNA: Protection of guanines by a nonspecifically bound disulfide

One-electron oxidation of DNA generates a base radical cation ("hole") that migrates through the duplex and causes damage at guanines. Unrepaired damage may lead to mutations. It has been suggested that "sacrificial guanines" in intron regions of DNA might serve to protect genes from damage. We have investigated the ability of a noncovalently bound sacrificial reagent to protect DNA from damage. Irradiation of an anthraquinone (AQ)-linked DNA duplex injects a radical cation into the DNA that causes reactions at GG steps close to and farther from the AQ. Bis[2-(3-(aminopropyl)amino)ethyl]disulfide, an analogue of spermine, binds to duplex DNA. Irradiation of the AQ-linked DNA in the presence of this disulfide suppresses the reaction at both GG steps and protects the DNA from damage. It is suggested that evolutionary pressure for the preservation of genomic integrity would yield disulfide-containing compounds optimized to bind to DNA and neutralize base radical cations. Copyright © 2002 American Chemical Society.