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Science 15 October 1999:
Vol. 286. no. 5439, pp. 552 - 555
DOI: 10.1126/science.286.5439.552
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Reports

Yeast Gene for a Tyr-DNA Phosphodiesterase that Repairs Topoisomerase I Complexes

Jeffrey J. Pouliot, Kevin C. Yao, Carol A. Robertson, Howard A. Nash *

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.

Laboratory of Molecular Biology, National Institute of Mental Health, Building 36, Room 1B08, Bethesda, MD 20892-4034, USA.
*   To whom correspondence should be addressed. E-mail: nash{at}codon.nih.gov

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