Citation | Mueller MM, Castells-Roca L, Babu V, Ermolaeva MA, Muller RU, Frommolt P, Williams AB, Greiss S, Schneider JI, Benzing T, Schermer B, Schumacher B. DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage. Nat Cell Biol, 2014. |
PubMed ID | 25419847 |
Short Description | DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage. GEO Record: GSE47778 GSE51161 GSE51162 Platform: GPL200 Download gene-centric, log2 transformed data: WBPaper00047070_1.ce.mr.csv |
# of Conditions | 15 |
Full Description | 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. Experimental Details: WBPaper00047070:N2_untreated_rep1 WBPaper00047070:N2_untreated_rep2 WBPaper00047070:N2_untreated_rep3 WBPaper00047070:N2_60mJ-UV_rep1 WBPaper00047070:N2_60mJ-UV_rep2 WBPaper00047070:N2_60mJ-UV_rep3 WBPaper00047070:N2_starvation_rep1 WBPaper00047070:N2_starvation_rep2 WBPaper00047070:N2_starvation_rep3 WBPaper00047070:xpa-1(ok698)_untreated_rep1 WBPaper00047070:xpa-1(ok698)_untreated_rep2 WBPaper00047070:xpa-1(ok698)_untreated_rep3 WBPaper00047070:xpa-1(ok698)_10mJ-UV_rep1 WBPaper00047070:xpa-1(ok698)_10mJ-UV_rep2 WBPaper00047070:xpa-1(ok698)_10mJ-UV_rep3. |
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