ABSTRACT
The major cytotoxic and mutagenic UV light-induced DNA photoproducts, cyclobutane pyrimidine dimers (CPDs) and (6-4) pyrimidine-pyrimidone photoproducts (6-4 PPs) have been and continue to be widely studied for characterizing DNA repair pathways and for elucidating the biological endpoints of unrepaired DNA damage. Early models for the recognition and initial enzymatic processing of UV lightinduced DNA damage included a direct endonucleolytic incision event occurring 50 to the site of the lesion followed by exonucleolytic removal of a DNA segment containing the damage, repair synthesis, and ligation (1). The notion of a single, direct acting 50-endonuclease capable of damage recognition and initiating DNA repair was abandoned following the discovery and characterization of the ATPdependent, 50 and 30-acting, dual incision nucleotide excision repair (NER) machinery in Escherichia coli, Saccharomyces cerevisiae, and humans (2,3). In addition, the discovery and characterization of a second major DNA excision repair pathway, the base excision repair (BER) pathway in numerous organisms which is initiated by various DNA N-glycosylases (4) further discouraged searches for additional excision repair proteins in prokaryotes or eukaryotes that might initiate the repair of a wide range of DNA damages. The discovery of a NER-independent alternative excision repair (AER) pathway for UV photoproducts in the fission yeast Schizosaccharomyces pombe led to the isolation and characterization of a remarkably diverse single protein, UV damage endonuclease (UVDE or Uvelp) that functions as a broad specificity, ATP-independent 50 endonuclease for initiating the repair of CPDs and 6-4 photoproducts (6-4 PPs) as well as a range of structurally heterogeneous DNA lesions. This chapter will emphasize the initial discovery, properties, substrate specificity, and cellular function of S. pombe UVDE in the AER pathway with its known components. A comparison of UVDE homologs from other organisms
will be made in order to gain insight into the regions of UVDE required for recognition and enzymatic processing of damaged DNA. Several earlier reviews have discussed various aspects of the S. pombe AER pathway (5-7). The AER pathway is also sometimes referred to as the UV damage excision repair (UVER) pathway (6).
