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 lead to cell death. Here, the isolation of the gene for an enzyme that can hydrolyze the bond between this protein and DNA is described. Enzyme-defective mutants of yeast are hypersensitive to treatments that increase the amount of covalent complexes, indicative of enzyme involvement in repair. The gene is conserved in eukaryotes and identifies a family of enzymes that has not been previously recognized. The presence of this gene in humans may have implications for the effectiveness of topoisomerase I poisons, such as the camptothecins, in chemotherapy.
Pouliot
J J
JJ
Laboratory of Molecular Biology, National Institute of Mental Health, Building 36, Room 1B08, Bethesda, MD 20892-4034, USA.
Yao
K C
KC
Robertson
C A
CA
Nash
H A
HA
D000595:Amino Acid Sequence; D000818:Animals; D002166:Camptothecin / Q000494:pharmacology; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000378:metabolism*; D020224:Expressed Sequence Tags; D005800:Genes, Fungal; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D016415:Sequence Alignment
D004271:DNA, Fungal; D010727:Phosphoric Diester Hydrolases; C498508:TDP1 protein, human; C122147:tyrosyl-DNA phosphodiesterase; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin