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dc.contributor.authorSvensson, J. Peter
dc.contributor.authorQuirós Pesudo, Laia
dc.contributor.authorMcRee, Siobhan K.
dc.contributor.authorAdeleye, Yeyejide A.
dc.contributor.authorCarmichael, Paul
dc.contributor.authorQuiros Pesudo, Laia
dc.contributor.authorSamson, Leona D
dc.date.accessioned2013-09-30T16:01:55Z
dc.date.available2013-09-30T16:01:55Z
dc.date.issued2013-09
dc.date.submitted2013-05
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1721.1/81239
dc.description.abstractToxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N′-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic ‘barcode’, were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput ‘barcode’ sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.en_US
dc.description.sponsorshipUnilever (Firm)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (R01-CA055042 (now R01-ES022872))en_US
dc.description.sponsorshipMassachusetts Institute of Technology. Center for Environmental Health Sciences (Grant NIEHS P30-ES002109)en_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pone.0073736en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en_US
dc.sourcePLoSen_US
dc.titleGenomic Phenotyping by Barcode Sequencing Broadly Distinguishes between Alkylating Agents, Oxidizing Agents, and Non-Genotoxic Agents, and Reveals a Role for Aromatic Amino Acids in Cellular Recovery after Quinone Exposureen_US
dc.typeArticleen_US
dc.identifier.citationSvensson, J. Peter, Laia Quirós Pesudo, Siobhan K. McRee, Yeyejide Adeleye, Paul Carmichael, and Leona D. Samson. “Genomic Phenotyping by Barcode Sequencing Broadly Distinguishes between Alkylating Agents, Oxidizing Agents, and Non-Genotoxic Agents, and Reveals a Role for Aromatic Amino Acids in Cellular Recovery after Quinone Exposure.” Edited by Martin G. Marinus. PLoS ONE 8, no. 9 (September 9, 2013): e73736.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Center for Environmental Health Sciencesen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorSamson, Leona D.en_US
dc.contributor.mitauthorQuiros Pesudo, Laiaen_US
dc.contributor.mitauthorSvensson, J. Peteren_US
dc.contributor.mitauthorMcRee, Siobhan K.en_US
dc.relation.journalPLoS ONEen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsSvensson, J. Peter; Quirós Pesudo, Laia; McRee, Siobhan K.; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7112-1454
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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