title: Tissue specific response to DNA damage: C. elegans as role model.
abstract: The various symptoms associated with hereditary defects in the DNA damage response (DDR), which range from developmental and neurological abnormalities and immunodeficiency to tissue-specific cancers and accelerated aging, suggest that DNA damage affects tissues differently. Mechanistic DDR studies are, however, mostly performed in vitro, in unicellular model systems or cultured cells, precluding a clear and comprehensive view of the DNA damage response of multicellular organisms. Studies performed in intact, multicellular animals models suggest that DDR can vary according to the type, proliferation and differentiation status of a cell. The nematode Caenorhabditis elegans has become an important DDR model and appears to be especially well suited to understand in vivo tissue-specific responses to DNA damage as well as the impact of DNA damage on development, reproduction and health of an entire multicellular organism. C. elegans germ cells are highly sensitive to DNA damage induction and respond via classical, evolutionary conserved DDR pathways aimed at efficient and error-free maintenance of the entire genome. Somatic tissues, however, respond differently to DNA damage and prioritize DDR mechanisms that promote growth and function. In this mini-review, we describe tissue-specific differences in DDR mechanisms that have been uncovered utilizing C. elegans as role model.
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Electronic address: w.lans@erasmusmc.nl.
authors.forename: Hannes
authors.initials: H
authors.lastname: Lans
authors.affiliation: Department of Genetics, Cancer Genomics Netherlands, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. Electronic address: w.vermeulen@erasmusmc.nl.
authors.forename: Wim
authors.initials: W
authors.lastname: Vermeulen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D059765:Homologous Recombination; D009928:Organ Specificity; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins
keywords: Base excision repair; C. elegans; DNA damage response; Homologous recombination; Interstrand-crosslink repair; Non-homologous end-joining; Nucleotide excision repair; Tissue specific