A prebiotic role for 8-oxoguanosine as a flavin mimic in pyrimidine dimer photorepair

Redox-active enzyme cofactors derived from ribonucleotides have been called "fossils of the RNA world," suggesting that early catalysts employed modified nucleobases to facilitate redox chemistry in primitive metabolism. Here, we show that the common oxidative damage product 8-oxo-7,8-dihydroguanine (OG), when incorporated into a DNA or RNA strand in proximity to a cyclobutane pyrimidine dimer, can mimic the function of a flavin in photorepair. The OG nucleotide acts catalytically in a mechanism consistent with that of photolyase in which the photoexcited state of the purine donates an electron to a pyrimidine dimer to initiate bond cleavage; subsequent back electron transfer regenerates OG. This unusual example of one form of DNA damage, oxidation, functioning to repair another, photodimerization, may provide insight into the origins of prebiotic redox processes.