Uve1p catalyzes the first step of an excision repair pathway in the fission yeast Schizosaccharomyces pombe that is genetically distinct from classical nucleotide and base excision repair. It was originally thought to cleave only at sites of UV light-induced damage, but in vitro studies have demonstrated that Uve1p can cleave at a variety of different DNA damages with varying levels of efficiency. The wide in vitro substrate specificity of Uve1p suggests that it could be interacting with other DNA repair pathways within the cell. Genetic evidence demonstrates that Uve1p efficiently processes base/base mismatches in vivo, including those that are poor cleavage substrates. Most DNA repair factors are present in some form of multi-protein complex or interaction. Furthermore, here are examples of protein-protein interactions that enhance the catalytic efficiency of DNA endonucleases. A series of experiments will be initiated to identify and characterize proteins that interact with Uve1p, with the ultimate goal of determining the full role that Uve1p provides in maintaining genomic in the cell.
