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Published on: February 24, 2014
More efficient repair of DNA double-strand breaks in skeletal muscle stem cells compared to their committed progeny
Leyla Vahidi Ferdousi1, Pierre Rocheteau2, Romain Chayot3
1Institut Pasteur, Yeast Molecular Genetics, Dept. of Genomes and Genetics, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France; CNRS UMR 3525, Team Stability of Nuclear and Mitochondrial DNA, Paris, France; Sorbonne Universités, UPMC, University of Paris 06, IFD-ED 515, Place Jussieu, Paris, 72252, France.
Abstract:
The loss of genome integrity in adult stem cells results in accelerated tissue aging and is possibly cancerogenic. Adult stem cells in different tissues appear to react robustly to DNA damage. We report that adult skeletal stem (satellite) cells do not primarily respond to radiation-induced DNA double-strand breaks (DSBs) via differentiation and exhibit less apoptosis compared to other myogenic cells. Satellite cells repair these DNA lesions more efficiently than their committed progeny. Importantly, non-proliferating satellite cells and post-mitotic nuclei in the fiber exhibit dramatically distinct repair efficiencies. Altogether, reduction of the repair capacity appears to be more a function of differentiation than of the proliferation status of the muscle cell. Notably, satellite cells retain a high efficiency of DSB repair also when isolated from the natural niche. Finally, we show that repair of DSB substrates is not only very efficient but, surprisingly, also very accurate in satellite cells and that accurate repair depends on the key non-homologous end-joining factor DNA-PKcs.
Insights
Adult skeletal stem cells efficiently repair DNA double-strand breaks (DSBs) with high accuracy, unlike differentiated cells. This robust DNA repair capacity is crucial for maintaining genome integrity and preventing aging and cancer.
Area of Science:
- Molecular Biology
- Stem Cell Biology
- Genetics
Background:
- Genome integrity loss in adult stem cells accelerates tissue aging and can lead to cancer.
- Adult stem cells typically exhibit robust responses to DNA damage.
Purpose of the Study:
- To investigate the DNA double-strand break (DSB) repair mechanisms in adult skeletal stem (satellite) cells.
- To compare the repair efficiency and accuracy of satellite cells with their differentiated progeny.
Main Methods:
- Exposure of satellite cells and myogenic cells to radiation-induced DSBs.
- Assessment of differentiation, apoptosis, and DSB repair efficiency.
- Evaluation of repair accuracy and dependence on DNA-PKcs.
Main Results:
- Satellite cells showed less apoptosis and did not primarily differentiate in response to DSBs.
- Satellite cells repaired DSBs more efficiently and accurately than their committed progeny.
- Repair efficiency was linked to differentiation status, not proliferation status, and remained high even when cells were isolated.
Conclusions:
- Adult skeletal stem cells possess a highly efficient and accurate DSB repair capacity, crucial for maintaining genome stability.
- Accurate repair is dependent on the non-homologous end-joining factor DNA-PKcs.
- This efficient repair mechanism in satellite cells may protect against age-related tissue degeneration and cancer.
Related Concept Videos
Satellite Stem Cells and Muscular Dystrophy
Fixing Double-strand Breaks
Fixing Double-strand Breaks
Homologous Recombination
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