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

被引:318
作者
Pouliot, JJ [1 ]
Yao, KC [1 ]
Robertson, CA [1 ]
Nash, HA [1 ]
机构
[1] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA
关键词
D O I
10.1126/science.286.5439.552
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 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.
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页码:552 / 555
页数:4
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