Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes

Covalent intermediates between topoisomerase I and DNA can become dead-end complexes that read to cell death. Here, the isolation of the gene for an e nzyme that can hydrolyze the bond between this protein and DNA is described . Enzyme-defective mutants of yeast are hypersensitive to treatments that i ncrease the amount of covalent complexes, indicative of enzyme involvement in repair. The gene is conserved in eukaryotes and identifies a family of e nzymes that has not been previously recognized. The presence of this gene i n humans may have implications for the effectiveness of topoisomerase I poi sons, such as the camptothecins, in chemotherapy.