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-...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/116772 https://orcid.org/0000-0002-4227-5163 https://orcid.org/0000-0002-1446-7256 |
| _version_ | 1826194548287602688 |
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| author | Reczek, Colleen R Birsoy, Kıvanç Kong, Hyewon Martínez-Reyes, Inmaculada Gao, Peng Chandel, Navdeep S Wang, Tim Sabatini, David |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Reczek, Colleen R Birsoy, Kıvanç Kong, Hyewon Martínez-Reyes, Inmaculada Gao, Peng Chandel, Navdeep S Wang, Tim Sabatini, David |
| author_sort | Reczek, Colleen R |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:57:57Z |
| format | Article |
| id | mit-1721.1/116772 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:57:57Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1167722022-09-26T14:53:01Z A CRISPR screen identifies a pathway required for paraquat-induced cell death Reczek, Colleen R Birsoy, Kıvanç Kong, Hyewon Martínez-Reyes, Inmaculada Gao, Peng Chandel, Navdeep S Wang, Tim Sabatini, David Koch Institute for Integrative Cancer Research at MIT Wang, Tim Sabatini, David 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. 2018-07-03T19:03:49Z 2018-07-03T19:03:49Z 2017-10 2016-12 2018-07-03T18:11:02Z Article http://purl.org/eprint/type/JournalArticle 1552-4450 1552-4469 http://hdl.handle.net/1721.1/116772 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 https://orcid.org/0000-0002-4227-5163 https://orcid.org/0000-0002-1446-7256 http://dx.doi.org/10.1038/NCHEMBIO.2499 Nature Chemical Biology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Reczek, Colleen R Birsoy, Kıvanç Kong, Hyewon Martínez-Reyes, Inmaculada Gao, Peng Chandel, Navdeep S Wang, Tim Sabatini, David A CRISPR screen identifies a pathway required for paraquat-induced cell death |
| title | A CRISPR screen identifies a pathway required for paraquat-induced cell death |
| title_full | A CRISPR screen identifies a pathway required for paraquat-induced cell death |
| title_fullStr | A CRISPR screen identifies a pathway required for paraquat-induced cell death |
| title_full_unstemmed | A CRISPR screen identifies a pathway required for paraquat-induced cell death |
| title_short | A CRISPR screen identifies a pathway required for paraquat-induced cell death |
| title_sort | crispr screen identifies a pathway required for paraquat induced cell death |
| url | http://hdl.handle.net/1721.1/116772 https://orcid.org/0000-0002-4227-5163 https://orcid.org/0000-0002-1446-7256 |
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