A CRISPR screen identifies a pathway required for paraquat-induced cell death

Paraquat, a herbicide linked to Parkinson's disease, generates reactive oxygen species (ROS), which causes cell death. Because the source of paraquat-induced ROS production remains unknown, we conducted a CRISPR-based positive-selection screen to identify metabolic genes essential for paraquat-...

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Bibliographic Details
Main Authors: Reczek, Colleen R (Author), Birsoy, Kıvanç (Author), Kong, Hyewon (Author), Martínez-Reyes, Inmaculada (Author), Gao, Peng (Author), Chandel, Navdeep S (Author), Wang, Tim (Contributor), Sabatini, David (Contributor)
Other Authors: Koch Institute for Integrative Cancer Research at MIT (Contributor)
Format: Article
Language:English
Published: Nature Publishing Group, 2018-07-03T19:03:49Z.
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Online Access:Get fulltext
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100 1 0 |a Reczek, Colleen R  |e author 
100 1 0 |a Koch Institute for Integrative Cancer Research at MIT  |e contributor 
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700 1 0 |a Kong, Hyewon  |e author 
700 1 0 |a Martínez-Reyes, Inmaculada  |e author 
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520 |a Paraquat, a herbicide linked to Parkinson's disease, generates reactive oxygen species (ROS), which causes cell death. Because the source of paraquat-induced ROS production remains unknown, we conducted a CRISPR-based positive-selection screen to identify metabolic genes essential for paraquat-induced cell death. Our screen uncovered three genes, POR (cytochrome P450 oxidoreductase), ATP7A (copper transporter), and SLC45A4 (sucrose transporter), required for paraquat-induced cell death. Furthermore, our results revealed POR as the source of paraquat-induced ROS production. Thus, our study highlights the use of functional genomic screens for uncovering redox biology. 
655 7 |a Article 
773 |t Nature Chemical Biology