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

Hui-Ling Ou, Christine S Kim, Simon Uszkoreit, Sara A Wickström, Björn Schumacher

Developmental cell 2019 Jul 22

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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. Copyright © 2019 Elsevier Inc. All rights reserved.

Citation

Hui-Ling Ou, Christine S Kim, Simon Uszkoreit, Sara A Wickström, Björn Schumacher. Somatic Niche Cells Regulate the CEP-1/p53-Mediated DNA Damage Response in Primordial Germ Cells. Developmental cell. 2019 Jul 22;50(2):167-183.e8