Universität zu Köln

Ermolaeva, Maria A., Segref, Alexandra ORCID: 0000-0001-8095-4469, Dakhovnik, Alexander, Ou, Hui-Ling, Schneider, Jennifer I., Utermoehlen, Olaf, Hoppe, Thorsten ORCID: 0000-0002-4734-9352 and Schumacher, Bjoern (2013). DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance. Nature, 501 (7467). S. 416 - 422. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ermolaeva, Maria A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Segref, Alexandra UNSPECIFIED orcid.org/0000-0001-8095-4469 UNSPECIFIED Dakhovnik, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Ou, Hui-Ling UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Jennifer I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-475805
DOI:	10.1038/nature12452
Journal or Publication Title:	Nature
Volume:	501
Number:	7467
Page Range:	S. 416 - 422
Date:	2013
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-4687
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CAENORHABDITIS-ELEGANS; C-ELEGANS; PATHWAY; ACTIVATION; EVOLUTION; INFECTION; APOPTOSIS; DAF-16 Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47580