E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells
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...
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todo:paper_15384101_v14_n8_p1300_Castillo2023-10-03T16:21:57Z E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells Castillo, D.S. Campalans, A. Belluscio, L.M. Carcagno, A.L. Radicell, J.P. Cánepa, E.T. Pregi, N. DNA damage response DNA repair E2F transcription factor Genomic stability Neuronal cells ATM protein ATR protein caspase 3 cycloheximide histone acetyltransferase GCN5 histone H2AX messenger RNA mitogen activated protein kinase kinase Rad51 protein transcription factor E2F1 transcription factor E2F2 zinostatin cycloheximide dactinomycin H2AFX protein, human histone histone acetyltransferase PCAF hydrogen peroxide mitogen activated protein kinase kinase kinase p300-CBP-associated factor protein synthesis inhibitor Rad51 protein transcription factor E2F1 transcription factor E2F2 animal cell apoptosis Article cell viability cellular stress response controlled study DNA damage DNA repair gene induction genetic transcription genomic instability genotoxicity histone acetylation human human cell mouse nerve cell nonhuman oxidative stress protein expression protein protein interaction protein synthesis radiation injury ultraviolet radiation upregulation cell survival cytology drug effects genetics HEK293 cell line metabolism nerve cell radiation response tumor cell line Cell Line, Tumor Cell Survival Cycloheximide Dactinomycin DNA Damage DNA Repair E2F1 Transcription Factor E2F2 Transcription Factor Genomic Instability HEK293 Cells Histones Humans Hydrogen Peroxide MAP Kinase Kinase Kinases Neurons p300-CBP Transcription Factors Protein Synthesis Inhibitors Rad51 Recombinase Ultraviolet Rays Up-Regulation 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 gH2AX 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. © 2015 Taylor & Francis Group, LLC Fil:Carcagno, A.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cánepa, E.T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pregi, N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15384101_v14_n8_p1300_Castillo |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
DNA damage response DNA repair E2F transcription factor Genomic stability Neuronal cells ATM protein ATR protein caspase 3 cycloheximide histone acetyltransferase GCN5 histone H2AX messenger RNA mitogen activated protein kinase kinase Rad51 protein transcription factor E2F1 transcription factor E2F2 zinostatin cycloheximide dactinomycin H2AFX protein, human histone histone acetyltransferase PCAF hydrogen peroxide mitogen activated protein kinase kinase kinase p300-CBP-associated factor protein synthesis inhibitor Rad51 protein transcription factor E2F1 transcription factor E2F2 animal cell apoptosis Article cell viability cellular stress response controlled study DNA damage DNA repair gene induction genetic transcription genomic instability genotoxicity histone acetylation human human cell mouse nerve cell nonhuman oxidative stress protein expression protein protein interaction protein synthesis radiation injury ultraviolet radiation upregulation cell survival cytology drug effects genetics HEK293 cell line metabolism nerve cell radiation response tumor cell line Cell Line, Tumor Cell Survival Cycloheximide Dactinomycin DNA Damage DNA Repair E2F1 Transcription Factor E2F2 Transcription Factor Genomic Instability HEK293 Cells Histones Humans Hydrogen Peroxide MAP Kinase Kinase Kinases Neurons p300-CBP Transcription Factors Protein Synthesis Inhibitors Rad51 Recombinase Ultraviolet Rays Up-Regulation |
| spellingShingle |
DNA damage response DNA repair E2F transcription factor Genomic stability Neuronal cells ATM protein ATR protein caspase 3 cycloheximide histone acetyltransferase GCN5 histone H2AX messenger RNA mitogen activated protein kinase kinase Rad51 protein transcription factor E2F1 transcription factor E2F2 zinostatin cycloheximide dactinomycin H2AFX protein, human histone histone acetyltransferase PCAF hydrogen peroxide mitogen activated protein kinase kinase kinase p300-CBP-associated factor protein synthesis inhibitor Rad51 protein transcription factor E2F1 transcription factor E2F2 animal cell apoptosis Article cell viability cellular stress response controlled study DNA damage DNA repair gene induction genetic transcription genomic instability genotoxicity histone acetylation human human cell mouse nerve cell nonhuman oxidative stress protein expression protein protein interaction protein synthesis radiation injury ultraviolet radiation upregulation cell survival cytology drug effects genetics HEK293 cell line metabolism nerve cell radiation response tumor cell line Cell Line, Tumor Cell Survival Cycloheximide Dactinomycin DNA Damage DNA Repair E2F1 Transcription Factor E2F2 Transcription Factor Genomic Instability HEK293 Cells Histones Humans Hydrogen Peroxide MAP Kinase Kinase Kinases Neurons p300-CBP Transcription Factors Protein Synthesis Inhibitors Rad51 Recombinase Ultraviolet Rays Up-Regulation Castillo, D.S. Campalans, A. Belluscio, L.M. Carcagno, A.L. Radicell, J.P. Cánepa, E.T. Pregi, N. E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells |
| topic_facet |
DNA damage response DNA repair E2F transcription factor Genomic stability Neuronal cells ATM protein ATR protein caspase 3 cycloheximide histone acetyltransferase GCN5 histone H2AX messenger RNA mitogen activated protein kinase kinase Rad51 protein transcription factor E2F1 transcription factor E2F2 zinostatin cycloheximide dactinomycin H2AFX protein, human histone histone acetyltransferase PCAF hydrogen peroxide mitogen activated protein kinase kinase kinase p300-CBP-associated factor protein synthesis inhibitor Rad51 protein transcription factor E2F1 transcription factor E2F2 animal cell apoptosis Article cell viability cellular stress response controlled study DNA damage DNA repair gene induction genetic transcription genomic instability genotoxicity histone acetylation human human cell mouse nerve cell nonhuman oxidative stress protein expression protein protein interaction protein synthesis radiation injury ultraviolet radiation upregulation cell survival cytology drug effects genetics HEK293 cell line metabolism nerve cell radiation response tumor cell line Cell Line, Tumor Cell Survival Cycloheximide Dactinomycin DNA Damage DNA Repair E2F1 Transcription Factor E2F2 Transcription Factor Genomic Instability HEK293 Cells Histones Humans Hydrogen Peroxide MAP Kinase Kinase Kinases Neurons p300-CBP Transcription Factors Protein Synthesis Inhibitors Rad51 Recombinase Ultraviolet Rays Up-Regulation |
| description |
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 gH2AX 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. © 2015 Taylor & Francis Group, LLC |
| format |
JOUR |
| author |
Castillo, D.S. Campalans, A. Belluscio, L.M. Carcagno, A.L. Radicell, J.P. Cánepa, E.T. Pregi, N. |
| author_facet |
Castillo, D.S. Campalans, A. Belluscio, L.M. Carcagno, A.L. Radicell, J.P. Cánepa, E.T. Pregi, N. |
| author_sort |
Castillo, D.S. |
| title |
E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells |
| title_short |
E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells |
| title_full |
E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells |
| title_fullStr |
E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells |
| title_full_unstemmed |
E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells |
| title_sort |
e2f1 and e2f2 induction in response to dna damage preserves genomic stability in neuronal cells |
| url |
http://hdl.handle.net/20.500.12110/paper_15384101_v14_n8_p1300_Castillo |
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