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Somatic Niche Cells Regulate the CEP-1/p53-Mediated DNA Damage Response in Primordial Germ Cells.
Ou, Hui-Ling; Kim, Christine S; Uszkoreit, Simon; Wickström, Sara A; Schumacher, Björn.
Afiliación
  • Ou HL; Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of
  • Kim CS; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Paul Gerson Unna Group "Skin Homeostasis and Ageing," Max Planck Institute for Biolog
  • Uszkoreit S; Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of
  • Wickström SA; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Paul Gerson Unna Group "Skin Homeostasis and Ageing," Max Planck Institute for Biolog
  • Schumacher B; Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of
Dev Cell ; 50(2): 167-183.e8, 2019 07 22.
Article en En | MEDLINE | ID: mdl-31336098
Genome integrity in primordial germ cells (PGCs) is a prerequisite for fertility and species maintenance. In C. elegans, PGCs require global-genome nucleotide excision repair (GG-NER) to remove UV-induced DNA lesions. Failure to remove the lesions leads to the activation of the C. elegans p53, CEP-1, resulting in mitotic arrest of the PGCs. We show that the eIF4E2 translation initiation factor IFE-4 in somatic gonad precursor (SGP) niche cells regulates the CEP-1/p53-mediated DNA damage response (DDR) in PGCs. We determine that the IFE-4 translation target EGL-15/FGFR regulates the non-cell-autonomous DDR that is mediated via FGF-like signaling. Using hair follicle stem cells as a paradigm, we demonstrate that the eIF4E2-mediated niche cell regulation of the p53 response in stem cells is highly conserved in mammals. We thus reveal that the somatic niche regulates the CEP-1/p53-mediated DNA damage checkpoint in PGCs. Our data suggest that the somatic niche impacts the stability of heritable genomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Proteína p53 Supresora de Tumor / Proteínas de Caenorhabditis elegans / Factores Eucarióticos de Iniciación / Factores de Crecimiento de Fibroblastos / Células Germinativas Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Proteína p53 Supresora de Tumor / Proteínas de Caenorhabditis elegans / Factores Eucarióticos de Iniciación / Factores de Crecimiento de Fibroblastos / Células Germinativas Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos