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DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage
Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility, and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates w...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250074/ https://www.ncbi.nlm.nih.gov/pubmed/25419847 http://dx.doi.org/10.1038/ncb3071 |
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author | Mueller, Michael M. Castells-Roca, Laia Babu, Vipin Ermolaeva, Maria A. Müller, Roman-Ulrich Frommolt, Peter Williams, Ashley B. Greiss, Sebastian Schneider, Jennifer I. Benzing, Thomas Schermer, Bernhard Schumacher, Björn |
author_facet | Mueller, Michael M. Castells-Roca, Laia Babu, Vipin Ermolaeva, Maria A. Müller, Roman-Ulrich Frommolt, Peter Williams, Ashley B. Greiss, Sebastian Schneider, Jennifer I. Benzing, Thomas Schermer, Bernhard Schumacher, Björn |
author_sort | Mueller, Michael M. |
collection | PubMed |
description | Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility, and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. 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. |
format | Online Article Text |
id | pubmed-4250074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-42500742015-06-01 DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage Mueller, Michael M. Castells-Roca, Laia Babu, Vipin Ermolaeva, Maria A. Müller, Roman-Ulrich Frommolt, Peter Williams, Ashley B. Greiss, Sebastian Schneider, Jennifer I. Benzing, Thomas Schermer, Bernhard Schumacher, Björn Nat Cell Biol Article Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility, and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. 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. 2014-11-24 2014-12 /pmc/articles/PMC4250074/ /pubmed/25419847 http://dx.doi.org/10.1038/ncb3071 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Mueller, Michael M. Castells-Roca, Laia Babu, Vipin Ermolaeva, Maria A. Müller, Roman-Ulrich Frommolt, Peter Williams, Ashley B. Greiss, Sebastian Schneider, Jennifer I. Benzing, Thomas Schermer, Bernhard Schumacher, Björn DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage |
title | DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage |
title_full | DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage |
title_fullStr | DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage |
title_full_unstemmed | DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage |
title_short | DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage |
title_sort | daf-16/foxo and egl-27/gata promote developmental growth in response to persistent somatic dna damage |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250074/ https://www.ncbi.nlm.nih.gov/pubmed/25419847 http://dx.doi.org/10.1038/ncb3071 |
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