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

Ou, H. L.; Kim, C. S.; Uszkoreit, S.; Wickström, S. A.; Schumacher, B.

doi:10.1016/j.devcel.2019.06.012

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

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Wickström, S. A.
Wickström – Skin Homeostasis and Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/31336098
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Citation

Ou, H. L., Kim, C. S., Uszkoreit, S., Wickström, S. A., & Schumacher, B. (2019). Somatic Niche Cells Regulate the CEP-1/p53-Mediated DNA Damage Response in Primordial Germ Cells. Dev Cell, 50(2), 167-183 e8. doi:10.1016/j.devcel.2019.06.012.

Cite as: https://hdl.handle.net/21.11116/0000-000B-41F4-8

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.