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Free keywords:
Animals
Apoptosis
Caenorhabditis elegans
Caenorhabditis elegans Proteins/genetics/*metabolism
Cells, Cultured
*DNA Damage
DNA Repair
Eukaryotic Initiation Factors/genetics/*metabolism
Female
Fibroblast Growth Factors/*metabolism
Germ Cells/metabolism/*pathology
Male
Mice
Mice, Inbred C57BL
Signal Transduction
Tumor Suppressor Protein p53/genetics/*metabolism
*cep-1
*Caenorhabditis elegans
*DNA damage response
*eIF4E2
*hair follicle stem cells
*ife-4
*nucleotide excision repair
*p53
*primordial germ cells
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.
