biostudies-literatureSugiyama TNIEHS NIH HHSNational Institutes of HealthNIGMS NIH HHS111762https://www.ebi.ac.uk/biostudies/studies/S-EPMC8671204biostudies-literatureUnknown823Although UV-induced mutagenesis has been studied extensively, the precise mechanisms that convert UV-induced DNA damage into mutations remain elusive. One well-studied mechanism involves DNA polymerase (Pol) η and ζ, which produces C > T transitions during translesion synthesis (TLS) across pyrimidine dimers. We previously proposed another biochemical mechanism that involves multiple UV-irradiations with incubation in the dark in between. The incubation facilitates spontaneous deamination of cytosine in a pyrimidine dimer, and the subsequent UV irradiation induces photolyase-independent (direct) photoreversal that converts cytosine into monomeric uracil residue. In this paper, we first demonstrate that natural sunlight can induce both mutational processes in vitro. The direct photoreversalMutation researchBiochemical and photochemical mechanisms that produce different UV-induced mutation spectra.PMC8671204R15ES029723R15 ES029723R15GM116098R15 GM116098Sanyal MRKeinard BSugiyama TBest GfalseBiochemical and photochemical mechanisms that produce different UV-induced mutation spectra.Although UV-induced mutagenesis has been studied extensively, the precise mechanisms that convert UV-induced DNA damage into mutations remain elusive. One well-studied mechanism involves DNA polymerase (Pol) η and ζ, which produces C > T transitions during translesion synthesis (TLS) across pyrimidine dimers. We previously proposed another biochemical mechanism that involves multiple UV-irradiations with incubation in the dark in between. The incubation facilitates spontaneous deamination of cytosine in a pyrimidine dimer, and the subsequent UV irradiation induces photolyase-independent (direct) photoreversal that converts cytosine into monomeric uracil residue. In this paper, we first demonstrate that natural sunlight can induce both mutational processes in vitro. The direct photoreversal2021-01-01T00:00:00Z2021 Jul-Dec2025-04-05T16:10:17.907Z2025-02-19T00:47:39.383ZS-EPMC86712043456379310.1016/j.mrfmmm.2021.111762