title: DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance.
abstract: DNA damage responses have been well characterized with regard to their cell-autonomous checkpoint functions leading to cell cycle arrest, senescence and apoptosis. In contrast, systemic responses to tissue-specific genome instability remain poorly understood. In adult Caenorhabditis elegans worms germ cells undergo mitotic and meiotic cell divisions, whereas somatic tissues are entirely post-mitotic. Consequently, DNA damage checkpoints function specifically in the germ line, whereas somatic tissues in adult C. elegans are highly radio-resistant. Some DNA repair systems such as global-genome nucleotide excision repair (GG-NER) remove lesions specifically in germ cells. Here we investigated how genome instability in germ cells affects somatic tissues in C. elegans. We show that exogenous and endogenous DNA damage in germ cells evokes elevated resistance to heat and oxidative stress. The somatic stress resistance is mediated by the ERK MAP kinase MPK-1 in germ cells that triggers the induction of putative secreted peptides associated with innate immunity. The innate immune response leads to activation of the ubiquitin-proteasome system (UPS) in somatic tissues, which confers enhanced proteostasis and systemic stress resistance. We propose that elevated systemic stress resistance promotes endurance of somatic tissues to allow delay of progeny production when germ cells are genomically compromised.
authors: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases, Institute for Genetics, University of Cologne, Zülpicher Strasse 47a, 50674 Cologne, Germany.
authors: Maria A
authors: MA
authors: Ermolaeva
authors: Alexandra
authors: A
authors: Segref
authors: Alexander
authors: A
authors: Dakhovnik
authors: Hui-Ling
authors: HL
authors: Ou
authors: Jennifer I
authors: JI
authors: Schneider
authors: Olaf
authors: O
authors: Utermöhlen
authors: Thorsten
authors: T
authors: Hoppe
authors: Björn
authors: B
authors: Schumacher
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D004789:Enzyme Activation; D042822:Genomic Instability / Q000235:genetics; D005854:Germ Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D006358:Hot Temperature; D007113:Immunity, Innate / Q000235:genetics; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D013312:Stress, Physiological / Q000276:immunology*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D025801:Ubiquitin; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans; D046988:Proteasome Endopeptidase Complex
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