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 i...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1999-10, Vol.286 (5439), p.552-555 |
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| creator | Pouliot, Jeffrey J. Yao, Kevin C. Robertson, Carol A. Nash, Howard A. |
| description | 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. |
| doi_str_mv | 10.1126/science.286.5439.552 |
| format | Article |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.286.5439.552</identifier><identifier>PMID: 10521354</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Amino Acid Sequence ; Animals ; Biological and medical sciences ; Camptothecin - pharmacology ; Cellular biology ; Deoxyribonucleic acid ; DNA ; DNA damage ; DNA Repair ; DNA topoisomerase I ; DNA Topoisomerases, Type I - genetics ; DNA Topoisomerases, Type I - metabolism ; DNA, Fungal - metabolism ; Enzymes ; Expressed Sequence Tags ; Fundamental and applied biological sciences. Psychology ; Genes ; Genes, Fungal ; Genetic aspects ; Genetic mutation ; Humans ; Lesions ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; Mutagenesis. Repair ; Mutation ; Narcotics ; Open reading frames ; Phosphoric Diester Hydrolases - chemistry ; Phosphoric Diester Hydrolases - genetics ; Phosphoric Diester Hydrolases - metabolism ; Physiological aspects ; Plasmids ; Polymerase chain reaction ; Proteins ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae - drug effects ; Saccharomyces cerevisiae - enzymology ; Saccharomyces cerevisiae - genetics ; Sequence Alignment ; Topoisomerase I ; Yeast ; Yeast (Food product) ; Yeasts</subject><ispartof>Science (American Association for the Advancement of Science), 1999-10, Vol.286 (5439), p.552-555</ispartof><rights>Copyright 1999 American Association for the Advancement of Science</rights><rights>1999 INIST-CNRS</rights><rights>COPYRIGHT 1999 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1999 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Oct 15, 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c794t-cf77b3e1a44c8df1994b1c7c0ba751e06d0c9c90c503a41a78e261a4a5b01233</citedby><cites>FETCH-LOGICAL-c794t-cf77b3e1a44c8df1994b1c7c0ba751e06d0c9c90c503a41a78e261a4a5b01233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2899330$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2899330$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>315,781,785,804,2885,2886,27929,27930,58022,58255</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1977347$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10521354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pouliot, Jeffrey J.</creatorcontrib><creatorcontrib>Yao, Kevin C.</creatorcontrib><creatorcontrib>Robertson, Carol A.</creatorcontrib><creatorcontrib>Nash, Howard A.</creatorcontrib><title>Yeast Gene for a Tyr-DNA Phosphodiesterase that Repairs Topoisomerase I Complexes</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Camptothecin - pharmacology</subject><subject>Cellular biology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA Repair</subject><subject>DNA topoisomerase I</subject><subject>DNA Topoisomerases, Type I - genetics</subject><subject>DNA Topoisomerases, Type I - metabolism</subject><subject>DNA, Fungal - metabolism</subject><subject>Enzymes</subject><subject>Expressed Sequence Tags</subject><subject>Fundamental and applied biological sciences. 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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.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>10521354</pmid><doi>10.1126/science.286.5439.552</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1999-10, Vol.286 (5439), p.552-555 |
| issn | 0036-8075 1095-9203 |
| language | eng |
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| source | MEDLINE; Science Magazine; JSTOR Archive Collection A-Z Listing |
| subjects | Amino Acid Sequence Animals Biological and medical sciences Camptothecin - pharmacology Cellular biology Deoxyribonucleic acid DNA DNA damage DNA Repair DNA topoisomerase I DNA Topoisomerases, Type I - genetics DNA Topoisomerases, Type I - metabolism DNA, Fungal - metabolism Enzymes Expressed Sequence Tags Fundamental and applied biological sciences. Psychology Genes Genes, Fungal Genetic aspects Genetic mutation Humans Lesions Molecular and cellular biology Molecular genetics Molecular Sequence Data Mutagenesis. Repair Mutation Narcotics Open reading frames Phosphoric Diester Hydrolases - chemistry Phosphoric Diester Hydrolases - genetics Phosphoric Diester Hydrolases - metabolism Physiological aspects Plasmids Polymerase chain reaction Proteins Saccharomyces cerevisiae Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - enzymology Saccharomyces cerevisiae - genetics Sequence Alignment Topoisomerase I Yeast Yeast (Food product) Yeasts |
| title | Yeast Gene for a Tyr-DNA Phosphodiesterase that Repairs Topoisomerase I Complexes |
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