Enzymatic photoreactivation: 50 years and counting

The discovery of enzymatic photoreactivation and of photolyase produced a p aradigm shift in the way investigators thought about the cellular consequen ces of DNA damage and about how these consequences could be avoided. The in vitro photoreactivation system, which utilized crude extracts from Sacchar omyces cerevisiae as the source of photolyase, not only provided informatio n about the mechanism of photoreactivation, but also played an important ro le in the discovery of nucleotide excision repair (NER) and the identificat ion of the pyrimidine dimer as the primary lethal lesion induced by 254 nm radiation, More recently, mechanistic studies using homogenous purified yea st photolyase have yielded insight into how DNA repair enzymes recognize sp ecific structures in DNA, while investigations looking at the repair of les ions 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-re sponsive transcriptional regulators. (C) 2000 Elsevier Science B.V. All rig hts reserved.