Source:http://linkedlifedata.com/resource/pubmed/id/19349972
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2009-4-8
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pubmed:abstractText |
We present a yeast chemical-genomics approach designed to identify genes that when mutated confer drug resistance, thereby providing insight about the modes of action of compounds. We developed a molecular barcoded yeast open reading frame (MoBY-ORF) library in which each gene, controlled by its native promoter and terminator, is cloned into a centromere-based vector along with two unique oligonucleotide barcodes. The MoBY-ORF resource has numerous genetic and chemical-genetic applications, but here we focus on cloning wild-type versions of mutant drug-resistance genes using a complementation strategy and on simultaneously assaying the fitness of all transformants with barcode microarrays. The complementation cloning was validated by mutation detection using whole-genome yeast tiling microarrays, which identified unique polymorphisms associated with a drug-resistant mutant. We used the MoBY-ORF library to identify the genetic basis of several drug-resistant mutants and in this analysis discovered a new class of sterol-binding compounds.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1546-1696
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pubmed:author |
pubmed-author:AndersenRaymond JRJ,
pubmed-author:AndrewsBrendaB,
pubmed-author:BarkerSarah LSL,
pubmed-author:BooneCharlesC,
pubmed-author:BotsteinDavidD,
pubmed-author:GiaeverGuriG,
pubmed-author:GrahamTodd RTR,
pubmed-author:GrayChristopher ACA,
pubmed-author:GreshamDavidD,
pubmed-author:HoCheuk HeiCH,
pubmed-author:KohJudice L YJL,
pubmed-author:MagtanongLeslieL,
pubmed-author:NatarajanParamasivamP,
pubmed-author:NishimuraShinichiS,
pubmed-author:NislowCoreyC,
pubmed-author:PorterJustinJ,
pubmed-author:YoshidaMinoruM
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pubmed:issnType |
Electronic
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
369-77
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pubmed:meshHeading | |
pubmed:year |
2009
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pubmed:articleTitle |
A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds.
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pubmed:affiliation |
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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