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Facioscapulohumeral dystrophy myoblasts efficiently repair moderate levels of oxidative DNA damage

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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.

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Acknowledgments

This research was supported by the MEGAFSHD grant from the Association Française contre les Myopathies (AFM) to YSV.

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Authors and Affiliations

  1. UMR 8126, CNRS, Univ. Paris-Sud, Institut de Cancérologie Gustave-Roussy, Université Paris Saclay, 94805, Villejuif, France

    Yara Bou Saada, Carla Dib, Petr Dmitriev, Marc Lipinski & Yegor S. Vassetzky

  2. INSERM U-1046, 371 Avenue du Doyen Gaston Giraud, 34295, Montpellier, France

    Gilles Carnac & Dalila Laoudj-Chenivesse

  3. ER030-EDST, Department of Life and Earth Sciences, Faculty of Sciences II, Lebanese University, Beirut, Lebanon

    Aline Hamade

  4. Koltzov Institute of Developmental Biology, Moscow, 117334, Russia

    Yegor S. Vassetzky

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  1. Yara Bou Saada
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Bou Saada, Y., Dib, C., Dmitriev, P. et al. Facioscapulohumeral dystrophy myoblasts efficiently repair moderate levels of oxidative DNA damage. Histochem Cell Biol 145, 475–483 (2016). https://doi.org/10.1007/s00418-016-1410-2

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