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dc.contributor.authorHerzog, Mareikeen
dc.contributor.authorPuddu, Fabioen
dc.contributor.authorCoates, Juliaen
dc.contributor.authorGeisler, Nicolaen
dc.contributor.authorForment, Josepen
dc.contributor.authorJackson, Stephenen
dc.date.accessioned2019-02-26T18:36:48Z
dc.date.available2019-02-26T18:36:48Z
dc.date.issued2018-04-18en
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/290009
dc.description.abstractGenetic and chemo-genetic interactions have played key roles in elucidating the molecular mechanisms by which certain chemicals perturb cellular functions. Many studies have employed gene knockout collections or gene disruption/depletion strategies to identify routes for evolving resistance to chemical agents. By contrast, searching for point-mutational genetic suppressors that can identify separation- or gain-of-function mutations, has been limited even in simpler, genetically amenable organisms such as yeast, and has not until recently been possible in mammalian cell culture systems. Here, by demonstrating its utility in identifying suppressors of cellular sensitivity to the drugs camptothecin or olaparib, we describe an approach allowing systematic, large-scale detection of spontaneous or chemically-induced suppressor mutations in yeast and in haploid mouse embryonic stem cells in a short timeframe, and with potential applications in essentially any other haploid system. In addition to its utility for molecular biology research, this protocol can be used to identify drug targets and to predict mechanisms leading to drug resistance. Mapping suppressor mutations on the primary sequence or three-dimensional structures of protein suppressor hits provides insights into functionally relevant protein domains, advancing our molecular understanding of protein functions, and potentially helping to improve drug design and applicability.
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleDetection of functional protein domains by unbiased genome-wide forward genetic screeningen
dc.typeArticle
prism.number6161en
prism.publicationDate2018en
prism.publicationNameScientific Reportsen
prism.volume8en
dc.identifier.doi10.17863/CAM.37236
dcterms.dateAccepted2018-03-22en
rioxxterms.versionofrecord10.1038/s41598-018-24400-4en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-04-18en
dc.contributor.orcidHerzog, Mareike [0000-0001-9747-2327]
dc.contributor.orcidPuddu, Fabio [0000-0002-2033-5209]
dc.contributor.orcidForment, Josep [0000-0002-7797-2583]
dc.contributor.orcidJackson, Stephen [0000-0001-9317-7937]
rioxxterms.typeJournal Article/Reviewen
cam.issuedOnline2018-04-18en
dc.identifier.urlhttps://www.nature.com/articles/s41598-018-24400-4#article-infoen


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International