Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage
Summary: Recent work established DNA replication stress as a crucial driver of genomic instability and a key event at the onset of cancer. Post-translational modifications play an important role in the cellular response to replication stress by regulating the activity of key components to prevent re...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716304636 |
| _version_ | 1818274167280107520 |
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| author | Cosetta Bertoli Anna E. Herlihy Betheney R. Pennycook Janos Kriston-Vizi Robertus A.M. de Bruin |
| author_facet | Cosetta Bertoli Anna E. Herlihy Betheney R. Pennycook Janos Kriston-Vizi Robertus A.M. de Bruin |
| author_sort | Cosetta Bertoli |
| collection | DOAJ |
| description | Summary: Recent work established DNA replication stress as a crucial driver of genomic instability and a key event at the onset of cancer. Post-translational modifications play an important role in the cellular response to replication stress by regulating the activity of key components to prevent replication-stress-induced DNA damage. Here, we establish a far greater role for transcriptional control in determining the outcome of replication-stress-induced events than previously suspected. Sustained E2F-dependent transcription is both required and sufficient for many crucial checkpoint functions, including fork stalling, stabilization, and resolution. Importantly, we also find that, in the context of oncogene-induced replication stress, where increased E2F activity is thought to cause replication stress, E2F activity is required to limit levels of DNA damage. These data suggest a model in which cells experiencing oncogene-induced replication stress through deregulation of E2F-dependent transcription become addicted to E2F activity to cope with high levels of replication stress. : Bertoli et al. establish a far greater role for transcriptional control in determining the outcome of replication-stress-induced events than previously suspected. Their data predict a model in which cells that experience oncogene-induced replication stress become addicted to E2F-dependent transcription to cope with high levels of replication stress. |
| first_indexed | 2024-12-12T22:09:33Z |
| format | Article |
| id | doaj.art-4ab6b935d351488b87d5dd3eafccf349 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T22:09:33Z |
| publishDate | 2016-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4ab6b935d351488b87d5dd3eafccf3492022-12-22T00:10:17ZengElsevierCell Reports2211-12472016-05-0115714121422Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA DamageCosetta Bertoli0Anna E. Herlihy1Betheney R. Pennycook2Janos Kriston-Vizi3Robertus A.M. de Bruin4MRC Laboratory for Molecular Cell Biology , University College London, London WC1E 6BT, UKMRC Laboratory for Molecular Cell Biology , University College London, London WC1E 6BT, UKMRC Laboratory for Molecular Cell Biology , University College London, London WC1E 6BT, UKMRC Laboratory for Molecular Cell Biology , University College London, London WC1E 6BT, UK; Bioinformatics Image Core (BIONIC) , University College London, London WC1E 6BT, UKMRC Laboratory for Molecular Cell Biology , University College London, London WC1E 6BT, UK; The UCL Cancer Institute, University College London, London WC1E 6BT, UK; Corresponding authorSummary: Recent work established DNA replication stress as a crucial driver of genomic instability and a key event at the onset of cancer. Post-translational modifications play an important role in the cellular response to replication stress by regulating the activity of key components to prevent replication-stress-induced DNA damage. Here, we establish a far greater role for transcriptional control in determining the outcome of replication-stress-induced events than previously suspected. Sustained E2F-dependent transcription is both required and sufficient for many crucial checkpoint functions, including fork stalling, stabilization, and resolution. Importantly, we also find that, in the context of oncogene-induced replication stress, where increased E2F activity is thought to cause replication stress, E2F activity is required to limit levels of DNA damage. These data suggest a model in which cells experiencing oncogene-induced replication stress through deregulation of E2F-dependent transcription become addicted to E2F activity to cope with high levels of replication stress. : Bertoli et al. establish a far greater role for transcriptional control in determining the outcome of replication-stress-induced events than previously suspected. Their data predict a model in which cells that experience oncogene-induced replication stress become addicted to E2F-dependent transcription to cope with high levels of replication stress.http://www.sciencedirect.com/science/article/pii/S2211124716304636 |
| spellingShingle | Cosetta Bertoli Anna E. Herlihy Betheney R. Pennycook Janos Kriston-Vizi Robertus A.M. de Bruin Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage Cell Reports |
| title | Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage |
| title_full | Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage |
| title_fullStr | Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage |
| title_full_unstemmed | Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage |
| title_short | Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage |
| title_sort | sustained e2f dependent transcription is a key mechanism to prevent replication stress induced dna damage |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716304636 |
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