title: DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
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.
authors.affiliation: Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Mueller
authors.affiliation: Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Laia
authors.initials: L
authors.lastname: Castells-Roca
authors.affiliation: Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Vipin
authors.initials: V
authors.lastname: Babu
authors.affiliation: Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ermolaeva
authors.affiliation: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany.
authors.forename: Roman-Ulrich
authors.initials: RU
authors.lastname: Müller
authors.affiliation: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Cologne Center for Genomics, University of Cologne, Weyertal 115b, 50931 Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Frommolt
authors.affiliation: Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Williams
authors.affiliation: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Greiss
authors.affiliation: Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Jennifer I
authors.initials: JI
authors.lastname: Schneider
authors.affiliation: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Benzing
authors.affiliation: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, 50937 Cologne, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schermer
authors.affiliation: Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.|Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Schumacher
mesh_terms: D000375:Aging; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D006540:Herbicides / Q000494:pharmacology; D010269:Paraquat / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C118081:EGL-27 protein, C elegans; D051858:Forkhead Transcription Factors; D006540:Herbicides; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D010269:Paraquat