10.6084/m9.figshare.1384857.v5
Daniela S Castillo
Daniela
S Castillo
Anna Campalans
Anna
Campalans
Laura M Belluscio
Laura
M Belluscio
Abel L Carcagno
Abel
L Carcagno
J Pablo Radicella
J
Pablo Radicella
Eduardo T Cánepa
Eduardo
T Cánepa
Nicolás Pregi
Nicolás
Pregi
E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells
Taylor & Francis Group
2015
DNA damage response
DNA repair
E2F transcription factor
genomic stability
neuronal cells
2015-10-12 21:45:29
Dataset
https://tandf.figshare.com/articles/dataset/E2F1_and_E2F2_induction_in_response_to_DNA_damage_preserves_genomic_stability_in_neuronal_cells/1384857
<p>E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which <i>E2F1</i> and <i>E2F2</i>, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of <i>de novo</i> protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.</p>