Singlet oxygen-mediated photocatalytic generation of abasic sites in DNA.

Oxidative stress factors such as light and inflammation are known to damage nucleic acids through various mechanisms. Guanine, among the four canonical nucleobases, is particularly susceptible to oxidation, leading to the formation of oxidatively generated lesions such as 8-oxo-7,8-dihydroguanine (8-oxoG), spiroiminodihydantoin (Sp), and guanidinohydantoin (Gh). In this study, we now report an abasic (AP) site generation from guanine residue oxidation based on photocatalytic reactions. The study used Dickerson-Drew dodecamer DNA as the model oligo DNA for photocatalytic reactions, and the reactions were analyzed using denaturing polyacrylamide gel electrophoresis, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, and ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry measurements. It was observed that guanine residues are converted into AP sites by reacting with singlet oxygen generated from the photocatalyst. Guanine residues with high solvent accessibility were found to be particularly reactive with singlet oxygen. Mechanistic investigations revealed that the photocatalytic generation of AP sites proceeds mainly via an 8-oxoG-independent mechanism. These findings are important for the design and development of photocatalyst-modified functional oligo probes and the understanding of their reactions.