期刊
NATURE CELL BIOLOGY
卷 16, 期 12, 页码 1168-U97出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3071
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资金
- NIH Office of Research Infrastructure Programs [P40OD010440]
- EMBO long-term fellowship
- Deutsche Forschungsgemeinschaft [SFB832, SCHE 1562/2]
- Deutsche Forschungsgemeinschaft (CECAD) [SFB 829, SFB 670, KFO 286]
- European Research Council (ERC Starting grant) [260383]
- Marie Curie (FP7 ITN) [316354, 316390, 316964, 239330]
- German-Israeli Foundation (GIF) [2213-1935.13/2008, 1104-68.11/2010]
- Deutsche Krebshilfe [109453]
- Bundesministerium fur Forschung und Bildung [FKZ0315893A-B]
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [P40OD010440] Funding Source: NIH RePORTER
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.
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