Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Mueller, Michael M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Castells-Roca, Laia UNSPECIFIED orcid.org/0000-0002-4604-9999 UNSPECIFIED Babu, Vipin UNSPECIFIED orcid.org/0000-0002-0001-8783 UNSPECIFIED Ermolaeva, Maria A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Roman-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Frommolt, Peter UNSPECIFIED orcid.org/0000-0002-1966-8014 UNSPECIFIED Williams, Ashley B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Greiss, Sebastian UNSPECIFIED orcid.org/0000-0001-9130-0831 UNSPECIFIED Schneider, Jennifer I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language NUCLEOTIDE EXCISION-REPAIR; CAENORHABDITIS-ELEGANS; C-ELEGANS; INDUCED APOPTOSIS; TRANSCRIPTION; PROTEIN; GENES; LONGEVITY; STRESS; NEMATODE Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42182