info:eu-repo/semantics/article
E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells
Fecha
2015-04Registro en:
Castillo, Daniela Susana; Campalans, Anna; Belluscio, Laura María; Carcagno, Abel Luis; Radicella, J. Pablo; et al.; E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells; Taylor & Francis; Cell Cycle; 14; 8; 4-2015; 1300-1314
1538-4101
CONICET Digital
CONICET
Autor
Castillo, Daniela Susana
Campalans, Anna
Belluscio, Laura María
Carcagno, Abel Luis
Radicella, J. Pablo
Canepa, Eduardo Tomas
Pregi, Nicolás
Resumen
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 E2F1 and E2F2, 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 de novo 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.