Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells
Open accessAbstract
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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KBM7 cells are a valid model to capture the overall essentiality profile of both ligases.
“KBM7 cells, which are a frequently used tool to study mechanisms of drug resistance are thus a valid model to capture the overall essentiality profile of both ligases. 28–30.”
From Functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders (2023) · cites this paper as [28]
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- Authors
- Forment, J. V., Herzog, M., Coates, J., Konopka, T., Gapp, B. V., Nijman, S. M., Adams, D. J., Keane, T. M., & Jackson, S. P.
- Affiliations
- University of Cambridge (GB)
- University of Oxford (GB)
- Austrian Academy of Sciences (AT)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Forment, Josep V
- Jackson, Stephen P
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2016-10-31
- Volume
- 13
- Issue
- 1
- Pages
- 12-14
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC5164930
- OpenAlex
- W2541984008
- Cited by
- 40
- References
- 35
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 8
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (092096/Z/10/Z, WT092096)
- Cancer Research UK (13031, 18796, 21717, 11224, A11224)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Genetic and Mutation Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- haploid embryonic stem cells, chemical mutagenesis, 6-thioguanine resistance, drug resistance, synthetic lethality, genetic interactions, mice
- MeSH terms
- Mouse Embryonic Stem Cells, Animals, Cell Line, Genetic Testing, Mutagenesis, Genome, Mice
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