2026-04-29T04:09:45Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65502024-11-29T23:07:10Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Mitxelena, Jone
author
Apraiz, Aintzane
author
Vallejo-Rodríguez, Jon
author
García-Santisteban, Iraia
author
Fullaondo, Asier
author
Alvarez Fernandez, Monica
author
Malumbres Martinez, Marcos
author
Zubiaga, Ana M
funder
Ministerio de Ciencia e Innovación (España)
funder
Basque Government (España)
funder
University of the Basque Country (España)
funder
Worldwide Cancer Research
2018-10-29T12:53:48Z
2018-10-29T12:53:48Z
2018-05-18
Nucleic Acids Res. 2018; 46 (9): 4546 - 4559.
0305-1048
http://hdl.handle.net/20.500.12105/6550
29590434
10.1093/nar/gky218
1362-4962
Nucleic acids research
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.
eng
CROSS-LINK REPAIR
NUCLEOTIDE EXCISION-REPAIR
FANCONI-ANEMIA PATHWAY
DOUBLE-STRAND BREAKS
CELL-CYCLE GENES
OMOLOGOUS RECOMBINATION
MELPHALAN RESISTANCE
MAMMALIAN-CELLS
E2F
SITES
An E2F7-dependent transcriptional program modulates DNA damage repair and genomic stability
journal article
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AnE2F7-dependenttranscriptional_2018.pdf
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AnE2F7-dependent transcriptionalgky218_2018_supp.pdf
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AnE2F7-dependenttranscriptional_2018.pdf.txt
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AnE2F7-dependent transcriptionalgky218_2018_supp.pdf.txt