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  A Systematic Mammalian Genetic Interaction Map Reveals Pathways Underlying Ricin Susceptibility

Bassik, M. C., Kampmann, M., Lebbink, R. J., Wang, S., Hein, M. Y., Poser, I., et al. (2013). A Systematic Mammalian Genetic Interaction Map Reveals Pathways Underlying Ricin Susceptibility. CELL, 152(4), 909-922. doi:10.1016/j.cell.2013.01.030.

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 Creators:
Bassik, Michael C.1, Author
Kampmann, Martin1, Author
Lebbink, Robert Jan1, Author
Wang, Shuyi1, Author
Hein, Marco Yannic2, Author              
Poser, Ina1, Author
Weibezahn, Jimena1, Author
Horlbeck, Max A.1, Author
Chen, Siyuan1, Author
Mann, Matthias2, Author              
Hyman, Anthony A.1, Author
LeProust, Emily M.1, Author
McManus, Michael T.1, Author
Weissman, Jonathan S.1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: ENDOPLASMIC-RETICULUM; TRANSLATION INITIATION; RETROGRADE TRANSPORT; SHRNA LIBRARIES; PROTEIN TOXINS; OVARIAN-CANCER; HUMAN-CELLS; E. COLI; RNAI; ORGANIZATION
 Abstract: Genetic interaction (GI) maps, comprising pairwise measures of how strongly the function of one gene depends on the presence of a second, have enabled the systematic exploration of gene function in microorganisms. Here, we present a two-stage strategy to construct high-density GI maps in mammalian cells. First, we use ultracomplex pooled shRNA libraries (25 shRNAs/gene) to identify high-confidence hit genes for a given phenotype and effective shRNAs. We then construct double-shRNA libraries from these to systematically measure GIs between hits. A GI map focused on ricin susceptibility broadly recapitulates known pathways and provides many unexpected insights. These include a noncanonical role for COPI, a previously uncharacterized protein complex affecting toxin clearance, a specialized role for the ribosomal protein RPS25, and functionally distinct mammalian TRAPP complexes. The ability to rapidly generate mammalian GI maps provides a potentially transformative tool for defining gene function and designing combination therapies based on synergistic pairs.

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Language(s): eng - English
 Dates: 2013-02-14
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: CELL
Source Genre: Journal
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Publ. Info: 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 152 (4) Sequence Number: - Start / End Page: 909 - 922 Identifier: ISSN: 0092-8674