| RRC ID |
59570
|
| Author |
Ou HL, Kim CS, Uszkoreit S, Wickström SA, Schumacher B.
|
| Title |
Somatic Niche Cells Regulate the CEP-1/p53-Mediated DNA Damage Response in Primordial Germ Cells.
|
| Journal |
Dev Cell
|
| 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.
|
| Volume |
50(2)
|
| Pages |
167-183.e8
|
| Published |
2019-7-22
|
| DOI |
10.1016/j.devcel.2019.06.012
|
| PII |
S1534-5807(19)30530-1
|
| PMID |
31336098
|
| MeSH |
Animals
Apoptosis
Caenorhabditis elegans
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Cells, Cultured
DNA Damage*
DNA Repair
Eukaryotic Initiation Factors / genetics
Eukaryotic Initiation Factors / metabolism*
Female
Fibroblast Growth Factors / metabolism*
Germ Cells / metabolism
Germ Cells / pathology*
Male
Mice
Mice, Inbred C57BL
Signal Transduction
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
|
| IF |
9.19
|
| Times Cited |
1
|
| Resource |
| C.elegans |
tm684
tm3886 |
