RRC ID |
30643
|
著者 |
Ermolaeva MA, Segref A, Dakhovnik A, Ou HL, Schneider JI, Utermöhlen O, Hoppe T, Schumacher B.
|
タイトル |
DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance.
|
ジャーナル |
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.
|
巻・号 |
501(7467)
|
ページ |
416-20
|
公開日 |
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 |
42.779
|
引用数 |
109
|
WOS 分野
|
GENETICS & HEREDITY
|
リソース情報 |
線虫 |
tm3886
tm853 |