Abstract
The ultraviolet component of sunlight induces two major DNA photoproducts linking two adjacent pyrimidines on one nucleotide strand: Cyclobutane Pyrimidine Dimers (CPD) and (6-4) Photoproducts. These photoproducts interrupt various life activities taking place on the DNA strands, such as transcription and replication. Photolyase is a unique DNA repair enzyme that uses blue light to reverse this UV-induced damage and restore the two parental pyrimidines. Many eukaryotes employ two functionally distinct photolyases, Class II CPD and (6-4) photolyases, to maintain genomic integrity, whereas most prokaryotes have a unique photolyase or photolyase-like gene, designated Class I CPD photolyase. Interestingly, despite their substrate differences, (6-4) photolyase is evolutionally closer to bacterial CPD photolyase, than either is to the eukaryote CPD photolyase. Studies on the prototypical bacterial CPD photolyase from Escherichia coli have been used to interpret the related functions of eukaryote photolyases, but many questions remain regarding the respective roles of these two photolyases in DNA repair in eukaryotes. To better understand the repair mechanisms and functional roles of photolyases in UV-tolerance in eukaryotes, we are applying and combining NMR, X-ray, structural modeling, phosphoramidite synthetic chemistry and molecular biochemistry to both eukaryotic photolyases. Here, we contrast the distinct substrate recognition and repair mechanisms of the two eukaryotic photolyases and discuss their potential roles in the DNA repair networks.
