title: More efficient repair of DNA double-strand breaks in skeletal muscle stem cells compared to their committed progeny.
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.
authors.affiliation: Institut 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.
authors.forename: Leyla
authors.initials: L
authors.lastname: Vahidi Ferdousi
authors.affiliation: Institut Pasteur, Stem Cells & Development, Dept. of Developmental and Stem Cell Biology, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France; CNRS URA 2578, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Rocheteau
authors.affiliation: Institut 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.
authors.forename: Romain
authors.initials: R
authors.lastname: Chayot
authors.affiliation: Institut 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.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Montagne
authors.affiliation: Institut 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.
authors.forename: Zayna
authors.initials: Z
authors.lastname: Chaker
authors.affiliation: Institut Pasteur, Stem Cells & Development, Dept. of Developmental and Stem Cell Biology, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France; CNRS URA 2578, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Flamant
authors.affiliation: Institut Pasteur, Stem Cells & Development, Dept. of Developmental and Stem Cell Biology, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France; CNRS URA 2578, Paris, France.
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
authors.affiliation: Institut 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. Electronic address: mricch@pasteur.fr.
authors.forename: Miria
authors.initials: M
authors.lastname: Ricchetti
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D059766:DNA End-Joining Repair; D005434:Flow Cytometry; D005720:Gamma Rays; D006657:Histones / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000528:radiation effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects
chemical_list: D006657:Histones