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Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage

Bertoli, C; Herlihy, AE; Pennycook, BR; Kriston-Vizi, J; De Bruin, RA; (2016) Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage. Cell Reports , 15 (7) pp. 1412-1422. 10.1016/j.celrep.2016.04.036. Green open access

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Abstract

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.

Type: Article
Title: Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2016.04.036
Publisher version: http://dx.doi.org/10.1016/j.celrep.2016.04.036
Language: English
Additional information: Copyright © 2016 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1494034
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