REPAIR OF UV-LIGHT INDUCED DNA LESIONS - A COMPARATIVE-STUDY WITH MODEL COMPOUNDS

DNA photolyases are enzymes that catalyze the light-dependend repair o f cis-syn-cyclobutane-thymine dimer UV lesions in a variety of organis ms. The basis of the repairreaction is an electron transfer from a red uced and deprotonated flavin cofactor to the dimer unit, which splits spontaneously as its radical anion. A second cofactor, which is either an 8-hydroxy-5-deazaflavin or a methenyl-tetrahydrofolate is required as a photo antenna and ensures efficient light absorption. With the h elp of model compounds that are able to mimic all crucial steps of the repair reaction, detailed mechanistic insights into the repair reacti on could be obtained. It became clear, that the enzyme requires the re duced flavin in its deprotonated form and that the repair reaction pro ceeds most efficiently in polar media, which is in agreement with the observed highly polar flavin binding pocket. Investigations with flavi n- and deazaflavin-containing model compounds confirmed that the deaza flavin functions solely as a photo antenna and allowed to study the de pendencies of the antenna function on the protonation state of the 8-h ydroxy-5-deazaflavin. The ability to mimic the repair reaction with sm all model compounds allowed finally the development of flavin cofactor functionalized oligopeptides. Cofactor peptides with the sequence of the DNA-binding domain of the transcription factor MyoD were shown to be able to repair UV light lesions of DNA within a DNA single strand.