Ou, Hui-Ling, Kim, Christine S., Uszkoreit, Simon, Wickstroem, Sara A. and Schumacher, Bjoern (2019). Somatic Niche Cells Regulate the CEP-1/p53-Mediated DNA Damage Response in Primordial Germ Cells. Dev. Cell, 50 (2). S. 167 - 192. CAMBRIDGE: CELL PRESS. ISSN 1878-1551

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ou, Hui-LingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kim, Christine S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uszkoreit, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wickstroem, Sara A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-134869
DOI: 10.1016/j.devcel.2019.06.012
Journal or Publication Title: Dev. Cell
Volume: 50
Number: 2
Page Range: S. 167 - 192
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1878-1551
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NUCLEOTIDE EXCISION-REPAIR; CAENORHABDITIS-ELEGANS; INDUCED APOPTOSIS; PROTEIN-SYNTHESIS; TRANSLATIONAL CONTROL; MESSENGER-RNAS; STEM-CELLS; P53; GROWTH; INITIATIONMultiple languages
Cell Biology; Developmental BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13486

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