title: Facioscapulohumeral dystrophy myoblasts efficiently repair moderate levels of oxidative DNA damage.
abstract: Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy linked to a deletion of a subset of D4Z4 macrosatellite repeats accompanied by a chromatin relaxation of the D4Z4 array on chromosome 4q. In vitro, FSHD primary myoblasts show altered expression of oxidative-related genes and are more susceptible to oxidative stress. Double homeobox 4 (DUX4) gene, encoded within each D4Z4 unit, is normally transcriptionally silenced but is found aberrantly expressed in skeletal muscles of FSHD patients. Its expression leads to a deregulation of DUX4 target genes including those implicated in redox balance. Here, we assessed DNA repair efficiency of oxidative DNA damage in FSHD myoblasts and DUX4-transfected myoblasts. We have shown that the DNA repair activity is altered neither in FSHD myoblasts nor in immortalized human myoblasts transiently expressing DUX4. DNA damage caused by moderate doses of an oxidant is efficiently repaired while FSHD myoblasts exposed for 24 h to high levels of oxidative stress accumulated more DNA damage than normal myoblasts, suggesting that FSHD myoblasts remain more vulnerable to oxidative stress at high doses of oxidants.
authors: UMR 8126, CNRS, Univ. Paris-Sud, Institut de Cancérologie Gustave-Roussy, Université Paris Saclay, 94805, Villejuif, France.
authors: Yara
authors: Y
authors: Bou Saada
authors: UMR 8126, CNRS, Univ. Paris-Sud, Institut de Cancérologie Gustave-Roussy, Université Paris Saclay, 94805, Villejuif, France.
authors: Carla
authors: C
authors: Dib
authors: UMR 8126, CNRS, Univ. Paris-Sud, Institut de Cancérologie Gustave-Roussy, Université Paris Saclay, 94805, Villejuif, France.
authors: Petr
authors: P
authors: Dmitriev
authors: ER030-EDST, Department of Life and Earth Sciences, Faculty of Sciences II, Lebanese University, Beirut, Lebanon.
authors: Aline
authors: A
authors: Hamade
authors: INSERM U-1046, 371 Avenue du Doyen Gaston Giraud, 34295, Montpellier, France.
authors: Gilles
authors: G
authors: Carnac
authors: INSERM U-1046, 371 Avenue du Doyen Gaston Giraud, 34295, Montpellier, France.
authors: Dalila
authors: D
authors: Laoudj-Chenivesse
authors: UMR 8126, CNRS, Univ. Paris-Sud, Institut de Cancérologie Gustave-Roussy, Université Paris Saclay, 94805, Villejuif, France.
authors: Marc
authors: M
authors: Lipinski
authors: UMR 8126, CNRS, Univ. Paris-Sud, Institut de Cancérologie Gustave-Roussy, Université Paris Saclay, 94805, Villejuif, France. vassetzky@igr.fr.|Koltzov Institute of Developmental Biology, Moscow, 117334, Russia. vassetzky@igr.fr.
authors: Yegor S
authors: http://orcid.org/0000-0003-3101-7043
authors: YS
authors: Vassetzky
mesh_terms: D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000378:metabolism* / Q000473:pathology; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: C121257:DUX4L1 protein, human; D018398:Homeodomain Proteins; D006861:Hydrogen Peroxide
keywords: DNA damage; DNA repair; DUX4; Facioscapulohumeral dystrophy; Oxidative stress