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

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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 ' , Developmental Cell , vol. 50 , no. 2 , pp. 167-+ . https://doi.org/10.1016/j.devcel.2019.06.012

Title: Somatic Niche Cells Regulate the CEP-1/p53-Mediated DNA Damage Response in Primordial Germ Cells
Author: Ou, Hui-Ling; Kim, Christine S.; Uszkoreit, Simon; Wickström, Sara A.; Schumacher, Björn
Other contributor: University of Helsinki, Helsinki Institute of Life Science HiLIFE, Joint Activities


Date: 2019-07-22
Language: eng
Number of pages: 25
Belongs to series: Developmental Cell
ISSN: 1534-5807
DOI: https://doi.org/10.1016/j.devcel.2019.06.012
URI: http://hdl.handle.net/10138/324356
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.
Subject: NUCLEOTIDE EXCISION-REPAIR
CAENORHABDITIS-ELEGANS
INDUCED APOPTOSIS
PROTEIN-SYNTHESIS
TRANSLATIONAL CONTROL
MESSENGER-RNAS
STEM-CELLS
P53
GROWTH
INITIATION
1182 Biochemistry, cell and molecular biology
1184 Genetics, developmental biology, physiology
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