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The cellular response to DNA damage, mediated by the DNA repair process, is essential in maintaining the integrity and stability of the genome. E2F-7 is an atypical member of the E2F family with a role in negatively regulating transcription and cell cycle progression under DNA damage. Surprisingly, we found that E2F-7 makes a transcription-independent contribution to the DNA repair process, which involves E2F-7 locating to and binding damaged DNA. Further, E2F-7 recruits CtBP and HDAC to the damaged DNA, altering the local chromatin environment of the DNA lesion. Importantly, the E2F-7 gene is a target for somatic mutation in human cancer and tumor-derived mutant alleles encode proteins with compromised transcription and DNA repair properties. Our results establish that E2F-7 participates in 2 closely linked processes, allowing it to directly couple the expression of genes involved in the DNA damage response with the DNA repair machinery, which has relevance in human malignancy.

Original publication

DOI

10.4161/cc.26078

Type

Journal article

Journal

Cell Cycle

Publication Date

15/09/2013

Volume

12

Pages

3037 - 3051

Keywords

DNA damage, DNA repair, E2F, somatic mutation, transcription, Alcohol Oxidoreductases, Alleles, Amino Acid Motifs, Cell Line, Tumor, DNA Damage, DNA Repair, DNA-Binding Proteins, E2F7 Transcription Factor, Histone Deacetylases, Histones, Homologous Recombination, Humans, Intracellular Signaling Peptides and Proteins, Mutation, Protein Binding, RNA Interference, RNA, Small Interfering, Transcription, Genetic, Tumor Suppressor p53-Binding Protein 1