A CRISPR screen identifies a pathway required for paraquat-induced cell death
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nihms907097.pdf
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1.12 MB
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Checksum (MD5)
19e4622cd3d2edf0659b02e4baab2aad
Author(s)
Reczek, Colleen R
Birsoy, Kıvanç
Kong, Hyewon
Martínez-Reyes, Inmaculada
Gao, Peng
Chandel, Navdeep S
Wang, Tim
Sabatini, David
Date Issued
October 2017
Journal
Nature Chemical Biology
Publisher
Nature Publishing Group
Citation
Reczek, Colleen R, Kıvanç Birsoy, Hyewon Kong, Inmaculada Martínez-Reyes, Tim Wang, Peng Gao, David M Sabatini, and Navdeep S Chandel. “A CRISPR Screen Identifies a Pathway Required for Paraquat-Induced Cell Death.” Nature Chemical Biology 13, 12 (October 2017): 1274–1279 © 2017 Nature America, Inc., part of Springer Nature
Version
Author's final manuscript
Abstract
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/NCHEMBIO.2499
