Yeast Gene for a Tyr-DNA Phosphodiesterase that Repairs Topoisomerase I Complexes
نویسندگان
چکیده
منابع مشابه
Antitumor Drug Camptothecin Lacking Yeast DNA Topoisomerase I: Restoration of Sensitivity Expression of Human DNA Topoisomerase I in Yeast Cells
Yeast Saccharomyces cerevisiae strains that are permeable to the antitumor alkaloid camptothecin are killed by the drug if they express DNA topoisomerase I, the cellular target of the drug (J. Nitiss and J. C. Wang, Proc. Nati. Acad. Sci. USA, «5.-7501-7505,1988). We show that in a yeast strain permeable to camptothecin but lacking DNA topoisom erase I, sensitivity to the drug was restored upo...
متن کاملExpression of yeast DNA topoisomerase I can complement a conditional-lethal DNA topoisomerase I mutation in Escherichia coli.
We show that, despite differences in primary structure, substrate preference, and mechanism of catalysis, yeast DNA topoisomerase I can functionally substitute for Escherichia coli DNA topoisomerase I. A family of plasmids expressing the yeast TOP1 gene or 5'-deletion mutations of it were used to complement the temperature-sensitive phenotype of an E. coli topA mutant. These plasmids were then ...
متن کاملHydrophilic camptothecin analogs that form extremely stable cleavable complexes with DNA and topoisomerase I.
Camptothecin (CPT) analogs that form more stable ternary complexes with DNA and topoisomerase I (termed cleavable complexes) show greater activity in their ability to inhibit tumor cell line growth in preclinical studies. Based on our earlier work, we hypothesized that analogs bearing hydrogen bonding moieties at the 7- through 10-position of CPT would result in more stable cleavable complexes....
متن کاملImmunodetection of human topoisomerase I-DNA covalent complexes
A number of established and investigational anticancer drugs slow the religation step of DNA topoisomerase I (topo I). These agents induce cytotoxicity by stabilizing topo I-DNA covalent complexes, which in turn interact with advancing replication forks or transcription complexes to generate lethal lesions. Despite the importance of topo I-DNA covalent complexes, it has been difficult to detect...
متن کاملAnalysis of topoisomerase I/DNA complexes in patients administered topotecan.
As part of a Phase II clinical trial of topotecan, DNA breakage in vivo was measured by detecting covalent topoisomerase/DNA intermediates in peripheral blood. The ICE (in vivo complex of enzyme) bioassay was used to assess topotecan activity in the peripheral blood of patients before, during, and after infusion therapy. The results can be summarized as: (a) ICE bioassay is a specific, antibody...
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ژورنال
عنوان ژورنال: Science
سال: 1999
ISSN: 0036-8075,1095-9203
DOI: 10.1126/science.286.5439.552