Mechanism of UV-induced Dewar lesion repair catalysed by DNA (6-4) photolyase

Chemical science, 2012, 3, 1794-1797 published on 02.04.2012
Chem. Sci.
UV irradiation of cellular DNA leads to the formation of mutagenic pyrimidine derived dimer lesions. One of the stable end products of the lesion forming pathways are DNA Dewar lesions. Here we report that the TpC derived Dewar lesions are efficiently repaired by the repair enzyme (6-4) photolyase, while the TpT derived Dewar lesion is unrepairable. We provide experimental and theoretical data showing that the substituent of the Dewar substructure is mainly responsible for this behavior. Studies with synthetic derivatives of the Dewar lesions and theory reveal how the substitution pattern of the important Dewar lesions governs their reparability.
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TU München