Paradoxical hotspots for guanine oxidation by a chemical mediator of inflammation

Guanine in DNA is a major oxidation target owing to its low ionization potential (IP), and there is often an inverse correlation between damage frequency and sequence-dependent variation in guanine IP. We report that the biological oxidant nitrosoperoxycarbonate (ONOOCO2-) paradoxically selects guanines with the highest IP in GC-containing contexts. Along with sequence-dependent variation in damage chemistry, this behavior points to factors other than charge migration as determinants of genomic DNA oxidation.