Can methylated purine bases act as photoionization hotspots?

The direct photoionization of DNA canonical bases under ultraviolet radiation is difficult due to the high ionization potentials. According to previous quantum chemical calculations, methylation can have great influence on the ionization potential. Are methylated nucleobases prone to photoionization and cause DNA damage? As an important epigenetic modification in transcription, expression, and regulation of genes, it is of great biological significance to explore the effect of methylation on base photoionization from the experimental perspective. Herein, we study the photoionization behavior of methylated purines 6 mA and 6mG at 266 nm using a nanosecond transient UV-Vis spectroscopy. The hydrated electron and methylated base radicals are observed, indicating the occurrence of photoionization for both 6mG and 6 mA. We measured one-photon ionization yields to be (5.0 ± 0.2) × 10^-3 and (1.4 ± 0.2) × 10^-3 for 6mG and 6 mA, respectively. These are higher than those of (dA)₂₀ and (dA₂₀ )·(dT₂₀ ) previously reported, indicating that methylation significantly promotes base photoionization with a stronger effect than base stacking, consistent with calculations in literature. Given that the hydrated electrons and methylated base radicals from photoionization can trigger a cascade of deleterious reactions, the methylated purine bases may act as hotspots of DNA photoionization damage of living organisms.