DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance

In Caenorhabditis elegans , genome instability in the form of exogenous and endogenous DNA damage in germ cells evokes elevated heat- and oxidative-stress resistance in somatic tissues; this is mediated by MPK-1, which triggers the induction of putative secreted peptides associated with innate immunity, leading to activation of the ubiquitin–proteasome system. A systemic response to DNA damage Björn Schumacher and colleagues have identified a systemic response to DNA damage in the roundworm Caenorhabditis elegans . They find that exogenous and endogenous DNA damage in germ cells induces stress resistance in somatic tissues cell non-autonomously. The process involves DNA-damage-induced activation of ERK MAPK signalling in germ cells and enhanced proteostasis associated with innate immunity in somatic tissues. DNA damage responses have been well characterized with regard to their cell-autonomous checkpoint functions leading to cell cycle arrest, senescence and apoptosis 1 . 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 2 , whereas somatic tissues in adult C. elegans are highly radio-resistant 3 . Some DNA repair systems such as global-genome nucleotide excision repair (GG-NER) remove lesions specifically in germ cells 4 . 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.