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Dev Cell. 2019 Jul 22;50(2):167-183.e8. doi: 10.1016/j.devcel.2019.06.012.

Somatic Niche Cells Regulate the CEP-1/p53-Mediated DNA Damage Response in Primordial Germ Cells.

Author information

1
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 Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
2
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 Biology of Ageing, Joseph-Stelzmann-Str. 9b, D-50931 Cologne, Germany.
3
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 Biology of Ageing, Joseph-Stelzmann-Str. 9b, D-50931 Cologne, Germany; Helsinki Institute of Life Science, Biomedicum Helsinki, University of Helsinki, FI-00014 Helsinki, Finland; Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, FI-00014 Helsinki, Finland.
4
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 Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany. Electronic address: bjoern.schumacher@uni-koeln.de.

Abstract

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.

KEYWORDS:

CEP-1; Caenorhabditis elegans; DNA damage response; eIF4E2; hair follicle stem cells; ife-4; nucleotide excision repair; p53; primordial germ cells

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