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Science. 2015 Nov 27;350(6264):1092-6. doi: 10.1126/science.aac7557. Epub 2015 Oct 15.

Gene essentiality and synthetic lethality in haploid human cells.

Author information

1
Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands.
2
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
3
Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA.
4
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. University of Montpellier, Institut de Recherche en Cancérologie de Montpellier Inserm U1194, Institut régional du Cancer Montpellier, 34000 Montpellier, France. jacques.colinge@inserm.fr gsuperti@cemm.at t.brummelkamp@nki.nl.
5
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. jacques.colinge@inserm.fr gsuperti@cemm.at t.brummelkamp@nki.nl.
6
Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. Cancer Genomics Center (CGC.nl), Plesmanlaan 121, 1066CX, Amsterdam, Netherlands. jacques.colinge@inserm.fr gsuperti@cemm.at t.brummelkamp@nki.nl.

Abstract

Although the genes essential for life have been identified in less complex model organisms, their elucidation in human cells has been hindered by technical barriers. We used extensive mutagenesis in haploid human cells to identify approximately 2000 genes required for optimal fitness under culture conditions. To study the principles of genetic interactions in human cells, we created a synthetic lethality network focused on the secretory pathway based exclusively on mutations. This revealed a genetic cross-talk governing Golgi homeostasis, an additional subunit of the human oligosaccharyltransferase complex, and a phosphatidylinositol 4-kinase β adaptor hijacked by viruses. The synthetic lethality map parallels observations made in yeast and projects a route forward to reveal genetic networks in diverse aspects of human cell biology.

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PMID:
26472760
DOI:
10.1126/science.aac7557
[Indexed for MEDLINE]
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