DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance
Open accessAbstract
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.
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The DNA damage response is a potent activator of inflammatory responses.
“The DDR is a potent activator of inflammatory responses.”
From The central role of DNA damage in the ageing process (2021) · cites this paper as [91]
DNA damage triggers innate immune responses that in C. elegans regulate systemic stress signaling.
“DNA damage triggers innate immune responses that in C. elegans regulate systemic stress signaling91.”
From The central role of DNA damage in the ageing process (2021) · cites this paper as [91]
DNA damage-driven inflammatory responses have been linked to aging in several organisms.
“Indeed, DNA damage-driven inflammatory responses have been linked to aging in several organisms (4,21).”
From Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability (2016) · cites this paper as [21]
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- Authors
- Ermolaeva, M. A., Segref, A., Dakhovnik, A., Ou, H.-L., Schneider, J. I., Utermöhlen, O., Hoppe, T., & Schumacher, B.
- Affiliations
- University of Cologne (DE)
- Corresponding author
- Schumacher, Björn
- ORCID
- Venue
- Nature
- Published
- 2013-08-25
- Volume
- 501
- Issue
- 7467
- Pages
- 416-420
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4120807
- OpenAlex
- W2084211225
- Cited by
- 221
- References
- 34
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 17 · 2023: 8 · 2022: 15 · 2021: 20 · 2020: 16 · 2019: 14 · 2018: 14 · 2017: 18 · 2016: 23 · 2015: 23 · 2014: 25 · 2013: 6
- FWCI
- 9.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (P40OD010440)
- Office of Research Infrastructure Programs, National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Keywords
- DNA damage, germ cells, genomic instability, innate immunity, MPK-1, ERK/MAPK signalling, secreted peptides, ubiquitin-proteasome system, proteostasis, oxidative stress resistance, heat stress resistance, Caenorhabditis elegans, somatic tissues, progeny production
- MeSH terms
- Adaptation, Physiological, Animals, DNA Damage, Enzyme Activation, Germ Cells, Hot Temperature, Immunity, Innate, Stress, Physiological, Caenorhabditis elegans, Oxidative Stress, Mitogen-Activated Protein Kinase 1, MAP Kinase Signaling System, Ubiquitin, Caenorhabditis elegans Proteins, Genomic Instability, Proteasome Endopeptidase Complex, Proteolysis
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