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  • 1
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    Haploid genetic screens in human cells identify host factors used by pathogens (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: Loss-of-function genetic screens in model organisms have elucidated numerous biological processes, but the diploid genome of mammalian cells has precluded large-scale gene disruption. We used insertional mutagenesis to develop a screening method to generate null alleles in a human cell line haploid for all chromosomes except chromosome 8. Using this approach, we identified host factors essential for infection with influenza and genes encoding important elements of the biosynthetic pathway of diphthamide, which are required for the cytotoxic effects of diphtheria toxin and exotoxin A. We also identified genes needed for the action of cytolethal distending toxin, including a cell-surface protein that interacts with the toxin. This approach has both conceptual and practical parallels with genetic approaches in haploid yeast.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carette, Jan E -- Guimaraes, Carla P -- Varadarajan, Malini -- Park, Annie S -- Wuethrich, Irene -- Godarova, Alzbeta -- Kotecki, Maciej -- Cochran, Brent H -- Spooner, Eric -- Ploegh, Hidde L -- Brummelkamp, Thijn R -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1231-5. doi: 10.1126/science.1178955.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965467" target="_blank"〉PubMed〈/a〉
    Keywords: ADP Ribose Transferases/metabolism/toxicity ; Adenosine Diphosphate Ribose/metabolism ; Amino Acid Sequence ; Antigens, Bacterial/metabolism/toxicity ; Bacterial Toxins/*metabolism/toxicity ; Biosynthetic Pathways ; Cell Line, Tumor ; Diphtheria Toxin/metabolism/toxicity ; Exotoxins/metabolism/toxicity ; Genes ; *Genetic Testing ; *Haploidy ; Histidine/analogs & derivatives/biosynthesis ; *Host-Pathogen Interactions ; Humans ; Influenza A Virus, H1N1 Subtype/*pathogenicity ; Molecular Sequence Data ; Monosaccharide Transport Proteins/genetics/metabolism ; Mutagenesis, Insertional ; N-Acylneuraminate Cytidylyltransferase/genetics/metabolism ; Peptide Elongation Factor 2/metabolism ; Proteins/chemistry/genetics/metabolism ; Virulence Factors/metabolism/toxicity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Gene essentiality and synthetic lethality in haploid human cells (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-10-17
    Description: 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 beta 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blomen, Vincent A -- Majek, Peter -- Jae, Lucas T -- Bigenzahn, Johannes W -- Nieuwenhuis, Joppe -- Staring, Jacqueline -- Sacco, Roberto -- van Diemen, Ferdy R -- Olk, Nadine -- Stukalov, Alexey -- Marceau, Caleb -- Janssen, Hans -- Carette, Jan E -- Bennett, Keiryn L -- Colinge, Jacques -- Superti-Furga, Giulio -- Brummelkamp, Thijn R -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1092-6. doi: 10.1126/science.aac7557. Epub 2015 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. ; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. ; Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA. ; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. University of Montpellier, Institut de Recherche en Cancerologie de Montpellier Inserm U1194, Institut regional du Cancer Montpellier, 34000 Montpellier, France. jacques.colinge@inserm.fr gsuperti@cemm.at t.brummelkamp@nki.nl. ; 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. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472760" target="_blank"〉PubMed〈/a〉
    Keywords: *Gene Regulatory Networks ; *Genes, Essential ; *Genes, Lethal ; Genetic Fitness/*genetics ; Golgi Apparatus/genetics ; *Haploidy ; Hexosyltransferases/genetics ; Humans ; Membrane Proteins/genetics ; Mutagenesis, Insertional ; Mutation ; Saccharomyces cerevisiae/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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    PAPER CURRENT
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