Instability of Trinucleotidic Repeats During Chromatin Remodeling in Spermatids |
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Authors: | Olivier Simard Marie‐Chantal Grégoire Mélina Arguin Marc‐André Brazeau Frédéric Leduc Isabelle Marois Martin V. Richter Guylain Boissonneault |
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Affiliation: | 1. Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Quebec, Canada;2. Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada |
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Abstract: | Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases. |
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Keywords: | double‐strand break genetic instability Huntington disease spermatid chromatin remodeling trinucleotide expansion Huntington HTT |
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