Gene essentiality and synthetic lethality in haploid human cells
Abstract
Zeroing in on essential human genes: More powerful genetic techniques are helping to define the list of genes required for the life of a human cell. Two papers used the CRISPR genome editing system and a gene trap method in haploid human cells to screen for essential genes (see the Perspective by Boone and Andrews). Wang et al. 's analysis of multiple cell lines indicates that it may be possible to find tumor-specific dependencies on particular genes. Blomen et al. investigate the phenomenon in which nonessential genes are required for fitness in the absence of another gene. Hence, complexity rather than robustness is the human strategy. Science , this issue p. 1096 and p. 1092 ; see also p. 1028
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Pooled CRISPR screening is a powerful and widely used method for identifying genes involved in biological mechanisms such as cell proliferation, drug resistance, and viral infection.
“Pooled CRISPR screening is a powerful and widely used method for identifying genes involved in biological mechanisms such as cell proliferation 1, 2 , drug resistance 3 , and viral infection 4 .”
From Pooled CRISPR screening with single-cell transcriptome readout. (2017) · cites this paper as [1]
Few, if any, bona fide hormone receptors are essential for the survival of Hap1 cells.
“However, few, if any, bona fide hormone receptors are essential for the survival of Hap1 cells (72, 73).”
From Massively parallel functional genomic assays in endocrinology: from promise to delivery (2026) · cites this paper as [72]
MAVEs in haploid cells are informed by well-curated lists of genes essential to survival of such cells.
“MAVEs in haploid cells are also informed by well-curated lists of genes which are essential to survival of such cells (72, 73).”
From Massively parallel functional genomic assays in endocrinology: from promise to delivery (2026) · cites this paper as [72]
Genome-scale application of CRISPR-Cas9 genome editing approaches offer the potential to map global genetic interaction networks in human cells.
“genome-scale application of CRISPR-Cas9 genome editing approaches offer the potential to map global genetic interaction networks in human cells (55–57)”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [57]
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- Authors
- Blomen, V. A., Májek, P., Jae, L. T., Bigenzahn, J. W., Nieuwenhuis, J., Staring, J., Sacco, R., van Diemen, F. R., Olk, N., Stukalov, A., Marceau, C., Janssen, H., Carette, J. E., Bennett, K. L., Colinge, J., Superti-Furga, G., & Brummelkamp, T. R.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Austrian Academy of Sciences (AT)
- Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands.
- Stanford Medicine (US)
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
- Corresponding author
- Blomen, Vincent A.
- Májek, Peter
- Jae, Lucas T.
- Colinge, Jacques
- Brummelkamp, Thijn R.
- ORCID
- Venue
- Science
- Published
- 2015-11-27
- Volume
- 350
- Issue
- 6264
- Pages
- 1092-1096
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2174686320
- Cited by
- 857
- References
- 9
- Citations by year
- 2026: 35 · 2025: 50 · 2024: 64 · 2023: 68 · 2022: 77 · 2021: 111 · 2020: 97 · 2019: 99 · 2018: 95 · 2017: 105 · 2016: 47 · 2015: 7
- FWCI
- 37.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Cancer Genomics Center
- European Research Council (ERC) (ERC-2012-StG 309634)
- Austrian Academy of Sciences
- Austrian Science Fund (FWF SFB F4711)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)
- ARC Foundation (PJA 20141201975)
- VIDI (91711316)
- Advanced ERC
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- gene essentiality, synthetic lethality, secretory pathway, oligosaccharyltransferase, genetic interactions, mutagenesis
- MeSH terms
- Genes, Lethal, Golgi Apparatus, Haploidy, Hexosyltransferases, Humans, Membrane Proteins, Mutation, Saccharomyces cerevisiae, Mutagenesis, Insertional, Genes, Essential, Gene Regulatory Networks, Genetic Fitness
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