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Learn MoreObjective: The E2F1 transcription factor regulates the expression of genes involved in cell proliferation, apoptosis and other cellular processes. In addition to regulating transcription, a number of studies have revealed novel, transcription-independent functions for E2F1 in regulating DNA repair. E2F1 localizes to sites of DNA damage dependent on its phosphorylation at serine 31 (serine 29 in mice) by the ATM or ATR kinases. In addition to phosphorylation, E2F1 is also acetylated in response to DNA damage on three lysine residues (K117, K120, and K125 in human E2F1), however how acetylation regulates the DNA repair function of E2F1 is unknown. To study the functional significance of E2F1 acetylation in DNA repair in vivo, we generated a targeted mutant mouse line in which the three sites of E2F1 acetylation were mutated from lysine to arginine and named this allele E2f1 3KR. RNA-seq analysis was performed on wild type and E2f1 3KR mouse embryonic fibroblasts (MEFs), before and after treatment with the radiomimetic drug neocarzinostatin (NCS), to examine the impact of the 3KR mutation on global gene expression patterns. SOURCE: David,G,JohnsonDr. Johnson University of Texas MD Anderson Cancer Center
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