Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells.
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Peer-reviewed
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Abstract
In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mutagenesis and next-generation sequencing, providing a new tool to explore mammalian genetic interactions.
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Keywords
Animals, Cell Line, Genetic Testing, Genome, Mice, Mouse Embryonic Stem Cells, Mutagenesis
Journal Title
Nature Chemical Biology
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1552-4450
1552-4469
1552-4469
Volume Title
13
Publisher
Springer Nature
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Sponsorship
Cancer Research UK (18796)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Cancer Research Uk (None)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Cancer Research Uk (None)
Research in the S.P.J. laboratory is funded by Cancer Research UK (CRUK; programme grant C6/A11224), the European Research Council and the European Community Seventh Framework Programme (grant agreement no. HEALTH-F2-2010-259893; DDResponse). Core funding is provided by Cancer Research UK (C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives salary from the University of Cambridge, supplemented by CRUK. J.V.F. was funded by Cancer Research UK programme grant C6/A11224 and the Ataxia Telangiectasia Society. J.C. was funded by Cancer Research UK programme grant C6/A11224. D.J.A. is supported by CRUK. Research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) and ERC grant agreement no. (311166).