RRC ID 30643
Author Ermolaeva MA, Segref A, Dakhovnik A, Ou HL, Schneider JI, Utermöhlen O, Hoppe T, Schumacher B.
Title DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance.
Journal Nature
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.
Volume 501(7467)
Pages 416-20
Published 2013-9-19
DOI 10.1038/nature12452
PII nature12452
PMID 23975097
PMC PMC4120807
MeSH Adaptation, Physiological / physiology* Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / immunology Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism DNA Damage* / genetics Enzyme Activation Genomic Instability / genetics Germ Cells / enzymology Germ Cells / immunology* Germ Cells / metabolism* Hot Temperature Immunity, Innate* / genetics MAP Kinase Signaling System Mitogen-Activated Protein Kinase 1 / metabolism Oxidative Stress Proteasome Endopeptidase Complex / metabolism Proteolysis Stress, Physiological / immunology* Ubiquitin / metabolism
IF 43.07
Times Cited 109
C.elegans tm3886 tm853