An E2F7-dependent transcriptional program modulates DNA damage repair and genomic stability
| Autor: | Mónica Álvarez-Fernández, Marcos Malumbres, Aintzane Apraiz, Asier Fullaondo, Ana M. Zubiaga, Jone Mitxelena, Iraia García-Santisteban, Jon Vallejo-Rodríguez |
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| Přispěvatelé: | Ministerio de Ciencia e Innovación (España), Basque Government (España), University of the Basque Country (España), Worldwide Cancer Research |
| Rok vydání: | 2018 |
| Předmět: |
nucleotide excision-repair
0301 basic medicine DNA Repair Transcription Genetic DNA repair DNA damage melphalan resistance mammalian-cells RAD51 homologous recombination Genome Integrity Repair and Replication fanconi-anemia pathway Biology Genomic Instability Cell Line 03 medical and health sciences E2F7 Transcription Factor E2F sites Genetics Transcriptional regulation Humans Promoter Regions Genetic cross-link repair double-strand breaks Cell Cycle OMOLOGOUS RECOMBINATION Recombinational DNA Repair cell-cycle genes Chromosome Breakage Cell cycle Cell biology 030104 developmental biology Gene Expression Regulation Tumor Suppressor Protein p53 Corrigendum Transcriptome Homologous recombination DNA Damage Nucleotide excision repair |
| Zdroj: | Addi. Archivo Digital para la Docencia y la Investigación instname Nucleic Acids Research Repisalud Instituto de Salud Carlos III (ISCIII) |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gky218 |
| Popis: | Corrigendum published on 03 July 2019 Nucleic Acids Research 47 (14) : 7716–7717 (2019) https://doi.org/10.1093/nar/gkz587 The cellular response to DNA damage is essential for maintaining the integrity of the genome. Recent evidence has identified E2F7 as a key player in DNA damage-dependent transcriptional regulation of cell-cycle genes. However, the contribution of E2F7 to cellular responses upon genotoxic damage is still poorly defined. Here we show that E2F7 represses the expression of genes involved in the maintenance of genomic stability, both throughout the cell cycle and upon induction of DNA lesions that interfere with replication fork progression. Knockdown of E2F7 leads to a reduction in 53BP1 and FANCD2 foci and to fewer chromosomal aberrations following treatment with agents that cause interstrand crosslink (ICL) lesions but not upon ionizing radiation. Accordingly, E2F7-depleted cells exhibit enhanced cell-cycle re-entry and clonogenic survival after exposure to ICL-inducing agents. We further report that expression and functional activity of E2F7 are p53-independent in this context. Using a cell-based assay, we show that E2F7 restricts homologous recombination through the transcriptional repression of RAD51. Finally, we present evidence that downregulation of E2F7 confers an increased resistance to chemotherapy in recombination-deficient cells. Taken together, our results reveal an E2F7-dependent transcriptional program that contributes to the regulation of DNA repair and genomic integrity. This work was supported by grants from the Spanish Ministry [SAF2012-33551 and SAF2015-67562-R, co-financed by FEDER funds, and SAF2014-57791-REDC], the Basque Government [IT634-13 and KK-2015/89], and the University of the Basque Country UPV/EHU [UFI11/20] to AMZ; and grants from the Spanish Ministry [SAF2015-69920-R], and Worldwide Cancer Research [15-0278] to MM. JM was recipient of a Basque Government fellowship for graduate studies and JVR is recipient of a UPV/EHU fellowship for graduate studies. M.A.F. was supported by a young investigator grant from MINECO [SAF2014-60442-JIN; co-financed by FEDER funds]. Funding for open access charge: Spanish Ministry [SAF2015-67562-R, co-financed by FEDER funds]; Basque Government [IT634-13]. |
| Databáze: | OpenAIRE |
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