Mueller, Michael M., Castells-Roca, Laia ORCID: 0000-0002-4604-9999, Babu, Vipin ORCID: 0000-0002-0001-8783, Ermolaeva, Maria A., Mueller, Roman-Ulrich, Frommolt, Peter ORCID: 0000-0002-1966-8014, Williams, Ashley B., Greiss, Sebastian ORCID: 0000-0001-9130-0831, Schneider, Jennifer I., Benzing, Thomas, Schermer, Bernhard ORCID: 0000-0002-5194-9000 and Schumacher, Bjoern (2014). DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage. Nat. Cell Biol., 16 (12). S. 1168 - 1192. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4679

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Mueller, Michael M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castells-Roca, LaiaUNSPECIFIEDorcid.org/0000-0002-4604-9999UNSPECIFIED
Babu, VipinUNSPECIFIEDorcid.org/0000-0002-0001-8783UNSPECIFIED
Ermolaeva, Maria A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Roman-UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frommolt, PeterUNSPECIFIEDorcid.org/0000-0002-1966-8014UNSPECIFIED
Williams, Ashley B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greiss, SebastianUNSPECIFIEDorcid.org/0000-0001-9130-0831UNSPECIFIED
Schneider, Jennifer I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDorcid.org/0000-0002-5194-9000UNSPECIFIED
Schumacher, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-421825
DOI: 10.1038/ncb3071
Journal or Publication Title: Nat. Cell Biol.
Volume: 16
Number: 12
Page Range: S. 1168 - 1192
Date: 2014
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-4679
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NUCLEOTIDE EXCISION-REPAIR; CAENORHABDITIS-ELEGANS; C-ELEGANS; INDUCED APOPTOSIS; TRANSCRIPTION; PROTEIN; GENES; LONGEVITY; STRESS; NEMATODEMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42182

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