DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage

Michael. M Mueller, Laia Castells-Roca, Vipin Babu, Maria A. Ermolaeva, Roman Ulrich Müller, Peter Frommolt, Ashley B. Williams, Sebastian Greiss, Jennifer I. Schneider, Thomas Benzing, Bernhard Schermer, Björn Schumacher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.

Original languageEnglish
Pages (from-to)1168-1179
JournalNature Cell Biology
Volume16
Issue number12
Early online date24 Nov 2014
DOIs
Publication statusPublished - 01 Dec 2014
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

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