title: The mef/elf4 transcription factor fine tunes the DNA damage response.
abstract: The ATM kinase plays a critical role in initiating the DNA damage response that is triggered by genotoxic stresses capable of inducing DNA double-strand breaks. Here, we show that ELF4/MEF, a member of the ETS family of transcription factors, contributes to the persistence of γH2AX DNA damage foci and promotes the DNA damage response leading to the induction of apoptosis. Conversely, the absence of ELF4 promotes the faster repair of damaged DNA and more rapid disappearance of γH2AX foci in response to γ-irradiation, leading to a radio-resistant phenotype despite normal ATM phosphorylation. Following γ-irradiation, ATM phosphorylates ELF4, leading to its degradation; a mutant form of ELF4 that cannot be phosphorylated by ATM persists following γ-irradiation, delaying the resolution of γH2AX foci and triggering an excessive DNA damage response. Thus, although ELF4 promotes the phosphorylation of H2AX by ATM, its activity must be dampened by ATM-dependent phosphorylation and degradation to avoid an excessive DNA damage response.
authors: Molecular Pharmacology and Chemistry Program of the Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors: Goro
authors: G
authors: Sashida
authors: Narae
authors: N
authors: Bae
authors: Silvana
authors: S
authors: Di Giandomenico
authors: Takashi
authors: T
authors: Asai
authors: Nadia
authors: N
authors: Gurvich
authors: Elena
authors: E
authors: Bazzoli
authors: Yan
authors: Y
authors: Liu
authors: Gang
authors: G
authors: Huang
authors: Xinyang
authors: X
authors: Zhao
authors: Silvia
authors: S
authors: Menendez
authors: Stephen D
authors: SD
authors: Nimer
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