A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest
© 2020 The Author(s) Cellular responses to stimuli can evolve over time, resulting in distinct early and late phases in response to a single signal. DNA damage induces a complex response that is largely orchestrated by the transcription factor p53, whose dynamics influence whether a damaged cell wil...
| Main Authors: | , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/133459 |
| _version_ | 1826205197697810432 |
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| author | Tsabar, Michael Mock, Caroline S Venkatachalam, Veena Reyes, Jose Karhohs, Kyle W Oliver, Trudy G Regev, Aviv Jambhekar, Ashwini Lahav, Galit |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Tsabar, Michael Mock, Caroline S Venkatachalam, Veena Reyes, Jose Karhohs, Kyle W Oliver, Trudy G Regev, Aviv Jambhekar, Ashwini Lahav, Galit |
| author_sort | Tsabar, Michael |
| collection | MIT |
| description | © 2020 The Author(s) Cellular responses to stimuli can evolve over time, resulting in distinct early and late phases in response to a single signal. DNA damage induces a complex response that is largely orchestrated by the transcription factor p53, whose dynamics influence whether a damaged cell will arrest and repair the damage or will initiate cell death. How p53 responses and cellular outcomes evolve in the presence of continuous DNA damage remains unknown. Here, we have found that a subset of cells switches from oscillating to sustained p53 dynamics several days after undergoing damage. The switch results from cell cycle progression in the presence of damaged DNA, which activates the caspase-2-PIDDosome, a complex that stabilizes p53 by inactivating its negative regulator MDM2. This work defines a molecular pathway that is activated if the canonical checkpoints fail to halt mitosis in the presence of damaged DNA. |
| first_indexed | 2024-09-23T13:08:56Z |
| format | Article |
| id | mit-1721.1/133459 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:08:56Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1334592023-11-03T15:32:50Z A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest Tsabar, Michael Mock, Caroline S Venkatachalam, Veena Reyes, Jose Karhohs, Kyle W Oliver, Trudy G Regev, Aviv Jambhekar, Ashwini Lahav, Galit Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Biology © 2020 The Author(s) Cellular responses to stimuli can evolve over time, resulting in distinct early and late phases in response to a single signal. DNA damage induces a complex response that is largely orchestrated by the transcription factor p53, whose dynamics influence whether a damaged cell will arrest and repair the damage or will initiate cell death. How p53 responses and cellular outcomes evolve in the presence of continuous DNA damage remains unknown. Here, we have found that a subset of cells switches from oscillating to sustained p53 dynamics several days after undergoing damage. The switch results from cell cycle progression in the presence of damaged DNA, which activates the caspase-2-PIDDosome, a complex that stabilizes p53 by inactivating its negative regulator MDM2. This work defines a molecular pathway that is activated if the canonical checkpoints fail to halt mitosis in the presence of damaged DNA. 2021-10-27T19:52:57Z 2021-10-27T19:52:57Z 2020 2021-07-22T16:30:34Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133459 en 10.1016/J.CELREP.2020.107995 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Tsabar, Michael Mock, Caroline S Venkatachalam, Veena Reyes, Jose Karhohs, Kyle W Oliver, Trudy G Regev, Aviv Jambhekar, Ashwini Lahav, Galit A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest |
| title | A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest |
| title_full | A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest |
| title_fullStr | A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest |
| title_full_unstemmed | A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest |
| title_short | A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest |
| title_sort | switch in p53 dynamics marks cells that escape from dsb induced cell cycle arrest |
| url | https://hdl.handle.net/1721.1/133459 |
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