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.

Stem Cell Research
|September 29, 2014
PubMed

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.

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