title: E2F-7 couples DNA damage-dependent transcription with the DNA repair process.
abstract: 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.
authors: Laboratory of Cancer Biology; Department of Oncology; University of Oxford; Oxford, UK.
authors: Lykourgos-Panagiotis
authors: LP
authors: Zalmas
authors: Amanda S
authors: AS
authors: Coutts
authors: Thomas
authors: T
authors: Helleday
authors: Nicholas B
authors: NB
authors: La Thangue
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000483:Alleles; D020816:Amino Acid Motifs; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D050702:E2F7 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014158:Transcription, Genetic; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D050702:E2F7 Transcription Factor; C481054:E2F7 protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D006655:Histone Deacetylases
keywords: DNA damage; DNA repair; E2F; somatic mutation; transcription
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