Abstract
Expansions of repetitive DNA sequences cause numerous human neurological and neuromuscular diseases. Ongoing repeat expansions in patients can exacerbate disease progression and severity. As pathogenesis is connected to repeat length, a potential therapeutic avenue is to modulate disease by manipulating repeat expansion size — targeting DNA, the root-cause of symptoms. How repeat instability is mediated by DNA replication, repair, recombination, transcription and epigenetics may explain its contribution to pathogenesis and give insights into therapeutic strategies to block expansions or induce contractions.
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Acknowledgements
We apologize to colleagues whose work could not be cited owing to size limitations. Many citations are included in Supplementary information S1 and S2. Work in the Pearson laboratory is supported by the Muscular Dystrophy Association, USA, the Canadian Institutes of Health Research (CIHR) and the University of Rochester Paul Wellstone Muscular Dystrophy Cooperative Research Center, with support from the National Institutes of Health (U54NS48843), a CIHR fellowship (JDC) and the Hospital for Sick Children Research Training Centre (ALC).
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López Castel, A., Cleary, J. & Pearson, C. Repeat instability as the basis for human diseases and as a potential target for therapy. Nat Rev Mol Cell Biol 11, 165–170 (2010). https://doi.org/10.1038/nrm2854
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DOI: https://doi.org/10.1038/nrm2854
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