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

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dc.contributor.author Ou, Hui-Ling
dc.contributor.author Kim, Christine S.
dc.contributor.author Uszkoreit, Simon
dc.contributor.author Wickström, Sara A.
dc.contributor.author Schumacher, Björn
dc.date.accessioned 2021-01-11T05:17:02Z
dc.date.available 2021-01-11T05:17:02Z
dc.date.issued 2019-07-22
dc.identifier.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 ' , Developmental Cell , vol. 50 , no. 2 , pp. 167-+ . https://doi.org/10.1016/j.devcel.2019.06.012
dc.identifier.other PURE: 127459722
dc.identifier.other PURE UUID: 0ef2e403-fd6a-4f84-9375-fe85a230edc9
dc.identifier.other WOS: 000476619600007
dc.identifier.uri http://hdl.handle.net/10138/324356
dc.description.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. en
dc.format.extent 25
dc.language.iso eng
dc.relation.ispartof Developmental Cell
dc.rights cc_by_nc_nd
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject NUCLEOTIDE EXCISION-REPAIR
dc.subject CAENORHABDITIS-ELEGANS
dc.subject INDUCED APOPTOSIS
dc.subject PROTEIN-SYNTHESIS
dc.subject TRANSLATIONAL CONTROL
dc.subject MESSENGER-RNAS
dc.subject STEM-CELLS
dc.subject P53
dc.subject GROWTH
dc.subject INITIATION
dc.subject 1182 Biochemistry, cell and molecular biology
dc.subject 1184 Genetics, developmental biology, physiology
dc.title Somatic Niche Cells Regulate the CEP-1/p53-Mediated DNA Damage Response in Primordial Germ Cells en
dc.type Article
dc.contributor.organization Helsinki Institute of Life Science HiLIFE, Joint Activities
dc.contributor.organization University of Helsinki
dc.contributor.organization Medicum
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1016/j.devcel.2019.06.012
dc.relation.issn 1534-5807
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion
dc.type.version publishedVersion

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