Enzymatic photoreactivation: 50 years and counting

The discovery of enzymatic photoreactivation and of photolyase produced a paradigm shift in the way investigators thought about the cellular consequences of DNA damage and about how these consequences could be avoided. The in vitro photoreactivation system, which utilized crude extracts from Saccharomyces cerevisiae as the source of photolyase, not only provided information about the mechanism of photoreactivation, but also played an important role in the discovery of nucleotide excision repair (NER) and the identification of the pyrimidine dimer as the primary lethal lesion induced by 254 nm radiation. More recently, mechanistic studies using homogenous purified yeast photolyase have yielded insight into how DNA repair enzymes recognize specific structures in DNA, while investigations looking at the repair of lesions in chromatin have begun to elucidate how DNA repair enzymes deal with damage in the context of eukaryotic chromosomes. Additionally, genetic and molecular studies of PHR1, the S. cerevisiae gene encoding the apoenzyme of photolyase, have led to the identification of previously unknown damage-responsive transcriptional regulators.