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Tissue specific response to DNA damage: C. elegans as role model
1Department of Genetics, Cancer Genomics Netherlands, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
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.
Insights
DNA damage response (DDR) varies across tissues in multicellular organisms. Studies in C. elegans reveal distinct DDR mechanisms in germ cells versus somatic tissues, impacting development and health.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- Hereditary defects in DNA damage response (DDR) cause diverse symptoms, including cancer and aging.
- In vitro studies limit understanding of DDR in complex multicellular organisms.
- Existing animal models suggest DDR varies by cell type and status.
Purpose of the Study:
- To review tissue-specific differences in DNA damage response (DDR) mechanisms.
- To highlight the utility of Caenorhabditis elegans as a model for in vivo DDR studies.
- To explore the impact of DNA damage on development, reproduction, and health in a whole organism.
Main Methods:
- Review of existing literature on DNA damage response (DDR) studies.
- Focus on research utilizing the nematode Caenorhabditis elegans as a model organism.
- Analysis of studies comparing DDR in germ cells versus somatic tissues.
Main Results:
- C. elegans germ cells are highly sensitive to DNA damage and employ conserved DDR pathways for genome maintenance.
- Somatic tissues in C. elegans exhibit different DDR strategies, prioritizing growth and function.
- These findings underscore significant tissue-specific variations in DDR within multicellular organisms.
Conclusions:
- Caenorhabditis elegans is a powerful model for dissecting in vivo, tissue-specific DNA damage responses.
- Understanding these differences is crucial for addressing diseases linked to DDR defects.
- DDR mechanisms are tailored to the specific roles and needs of different cell types.
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