Replication stress promotes cell elimination by extrusion
Cell extrusion is a mechanism of cell elimination that is used by organisms as diverse as sponges, nematodes, insects and mammals1-3. During extrusion, a cell detaches from a layer of surrounding cells while maintaining the continuity of that layer4. Vertebrate epithelial tissues primarily eliminate...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/131223 |
| _version_ | 1826212006856753152 |
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| author | Dwivedi, Vivek Kumar Pardo-Pastor, Carlos Droste, Rita Kong, Ji Na Tucker, Nolan Denning, Daniel Prudden Rosenblatt, Jody Horvitz, Howard Robert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Dwivedi, Vivek Kumar Pardo-Pastor, Carlos Droste, Rita Kong, Ji Na Tucker, Nolan Denning, Daniel Prudden Rosenblatt, Jody Horvitz, Howard Robert |
| author_sort | Dwivedi, Vivek Kumar |
| collection | MIT |
| description | Cell extrusion is a mechanism of cell elimination that is used by organisms as diverse as sponges, nematodes, insects and mammals1-3. During extrusion, a cell detaches from a layer of surrounding cells while maintaining the continuity of that layer4. Vertebrate epithelial tissues primarily eliminate cells by extrusion, and the dysregulation of cell extrusion has been linked to epithelial diseases, including cancer1,5. The mechanisms that drive cell extrusion remain incompletely understood. Here, to analyse cell extrusion by Caenorhabditis elegans embryos3, we conducted a genome-wide RNA interference screen, identified multiple cell-cycle genes with S-phase-specific function, and performed live-imaging experiments to establish how those genes control extrusion. Extruding cells experience replication stress during S phase and activate a replication-stress response via homologues of ATR and CHK1. Preventing S-phase entry, inhibiting the replication-stress response, or allowing completion of the cell cycle blocked cell extrusion. Hydroxyurea-induced replication stress6,7 triggered ATR-CHK1- and p53-dependent cell extrusion from a mammalian epithelial monolayer. We conclude that cell extrusion induced by replication stress is conserved among animals and propose that this extrusion process is a primordial mechanism of cell elimination with a tumour-suppressive function in mammals. |
| first_indexed | 2024-09-23T15:15:00Z |
| format | Article |
| id | mit-1721.1/131223 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:15:00Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1312232022-10-02T01:38:01Z Replication stress promotes cell elimination by extrusion Dwivedi, Vivek Kumar Pardo-Pastor, Carlos Droste, Rita Kong, Ji Na Tucker, Nolan Denning, Daniel Prudden Rosenblatt, Jody Horvitz, Howard Robert Massachusetts Institute of Technology. Department of Biology Cell extrusion is a mechanism of cell elimination that is used by organisms as diverse as sponges, nematodes, insects and mammals1-3. During extrusion, a cell detaches from a layer of surrounding cells while maintaining the continuity of that layer4. Vertebrate epithelial tissues primarily eliminate cells by extrusion, and the dysregulation of cell extrusion has been linked to epithelial diseases, including cancer1,5. The mechanisms that drive cell extrusion remain incompletely understood. Here, to analyse cell extrusion by Caenorhabditis elegans embryos3, we conducted a genome-wide RNA interference screen, identified multiple cell-cycle genes with S-phase-specific function, and performed live-imaging experiments to establish how those genes control extrusion. Extruding cells experience replication stress during S phase and activate a replication-stress response via homologues of ATR and CHK1. Preventing S-phase entry, inhibiting the replication-stress response, or allowing completion of the cell cycle blocked cell extrusion. Hydroxyurea-induced replication stress6,7 triggered ATR-CHK1- and p53-dependent cell extrusion from a mammalian epithelial monolayer. We conclude that cell extrusion induced by replication stress is conserved among animals and propose that this extrusion process is a primordial mechanism of cell elimination with a tumour-suppressive function in mammals. NIH (Grants R01GM024663 and T32GM007287) 2021-08-31T15:34:05Z 2021-08-31T15:34:05Z 2021-05 2019-12 2021-08-24T14:20:29Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 https://hdl.handle.net/1721.1/131223 Dwivedi, Vivek K. et al. "Replication stress promotes cell elimination by extrusion." Nature 593, 7860 (May 2021): 591–596. © 2021 The Author(s) en http://dx.doi.org/10.1038/s41586-021-03526-y Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media LLC Prof. Horvitz |
| spellingShingle | Dwivedi, Vivek Kumar Pardo-Pastor, Carlos Droste, Rita Kong, Ji Na Tucker, Nolan Denning, Daniel Prudden Rosenblatt, Jody Horvitz, Howard Robert Replication stress promotes cell elimination by extrusion |
| title | Replication stress promotes cell elimination by extrusion |
| title_full | Replication stress promotes cell elimination by extrusion |
| title_fullStr | Replication stress promotes cell elimination by extrusion |
| title_full_unstemmed | Replication stress promotes cell elimination by extrusion |
| title_short | Replication stress promotes cell elimination by extrusion |
| title_sort | replication stress promotes cell elimination by extrusion |
| url | https://hdl.handle.net/1721.1/131223 |
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