The Mef/Elf4 transcription factor fine tunes the DNA damage response

Goro Sashida, Narae Bae, Silvana Di Giandomenico, Takashi Asai, Nadia Gurvich, Elena Bazzoli, Yan Liu, Gang Huang, Xinyang Zhao, Silvia Menendez, Stephen D. Nimer

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4857-4865
Number of pages9
JournalCancer Research
Volume71
Issue number14
DOIs
Publication statusPublished - Jul 15 2011

Fingerprint

DNA Damage
Transcription Factors
Phosphorylation
Double-Stranded DNA Breaks
Radio
DNA Repair
Phosphotransferases
Apoptosis
Phenotype

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sashida, G., Bae, N., Di Giandomenico, S., Asai, T., Gurvich, N., Bazzoli, E., ... Nimer, S. D. (2011). The Mef/Elf4 transcription factor fine tunes the DNA damage response. Cancer Research, 71(14), 4857-4865. https://doi.org/10.1158/0008-5472.CAN-11-0455

The Mef/Elf4 transcription factor fine tunes the DNA damage response. / Sashida, Goro; Bae, Narae; Di Giandomenico, Silvana; Asai, Takashi; Gurvich, Nadia; Bazzoli, Elena; Liu, Yan; Huang, Gang; Zhao, Xinyang; Menendez, Silvia; Nimer, Stephen D.

In: Cancer Research, Vol. 71, No. 14, 15.07.2011, p. 4857-4865.

Research output: Contribution to journalArticle

Sashida, G, Bae, N, Di Giandomenico, S, Asai, T, Gurvich, N, Bazzoli, E, Liu, Y, Huang, G, Zhao, X, Menendez, S & Nimer, SD 2011, 'The Mef/Elf4 transcription factor fine tunes the DNA damage response', Cancer Research, vol. 71, no. 14, pp. 4857-4865. https://doi.org/10.1158/0008-5472.CAN-11-0455
Sashida G, Bae N, Di Giandomenico S, Asai T, Gurvich N, Bazzoli E et al. The Mef/Elf4 transcription factor fine tunes the DNA damage response. Cancer Research. 2011 Jul 15;71(14):4857-4865. https://doi.org/10.1158/0008-5472.CAN-11-0455
Sashida, Goro ; Bae, Narae ; Di Giandomenico, Silvana ; Asai, Takashi ; Gurvich, Nadia ; Bazzoli, Elena ; Liu, Yan ; Huang, Gang ; Zhao, Xinyang ; Menendez, Silvia ; Nimer, Stephen D. / The Mef/Elf4 transcription factor fine tunes the DNA damage response. In: Cancer Research. 2011 ; Vol. 71, No. 14. pp. 4857-4865.
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