title: The (6-4) Dimeric Lesion as a DNA Photosensitizer.
abstract: Based on our previous investigations into the photophysical properties of the 5-methyl-2-pyrimidone (Pyo) chromophore, we now extend our studies to the photobehavior of the dimeric (6-4) thymine photoproducts (6-4 PP) to evaluate their capability to act as instrinsic DNA photosensitizers. The lesion presents significant absorption in the UVB/UVA region, weak fluorescence emission, a singlet-excited-state energy of approximately 351 kJ mol(-1) , and a triplet-excited-state energy of 297 kJ mol(-1) . Its triplet transient absorption has a maximum at 420-440 nm, a lifetime of around 7 μs, and a high formation quantum yield, ΦISC =0.86. This species is efficiently quenched by thymidine. Its DNA photosensitizing properties are demonstrated by a series of experiments run on a pBR322 plasmid. The lesion photoinduces both single-strand breaks and the formation of cyclobutane thymine dimers. Altogether, these results show that, the substitution of the pyrimidone ring at C4 by a 5-hydroxy-5,6-dihydrothymine does not cancel out the photosensitization properties of the chromophore.
authors.affiliation: Consejo Superior de Investigaciones Científicas, Universitat Politècnica de València, Avenida de los Naranjos s/n, 46022, Valencia, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Vendrell-Criado
authors.affiliation: Consejo Superior de Investigaciones Científicas, Universitat Politècnica de València, Avenida de los Naranjos s/n, 46022, Valencia, Spain.
authors.forename: Gemma M
authors.initials: GM
authors.lastname: Rodríguez-Muñiz
authors.affiliation: Consejo Superior de Investigaciones Científicas, Universitat Politècnica de València, Avenida de los Naranjos s/n, 46022, Valencia, Spain.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lhiaubet-Vallet
authors.affiliation: Consejo Superior de Investigaciones Científicas, Universitat Politècnica de València, Avenida de los Naranjos s/n, 46022, Valencia, Spain. mmiranda@qim.upv.es.
authors.forename: M Consuelo
authors.initials: MC
authors.lastname: Cuquerella
authors.affiliation: Consejo Superior de Investigaciones Científicas, Universitat Politècnica de València, Avenida de los Naranjos s/n, 46022, Valencia, Spain. mcuquere@itq.upv.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Miranda
mesh_terms: D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D019281:Dimerization; D007834:Lasers; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D017319:Photosensitizing Agents; D011744:Pyrimidinones; C056905:5-methyl-2-pyrimidinone; D004247:DNA
keywords: DNA damage; cyclobutane pyrimidine dimers; photochemistry; pyrimidone; triplet excited states