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Instability of trinucleotidic repeats during chromatin remodeling in spermatids.

Human mutation (2014-08-20)
Olivier Simard, Marie-Chantal Grégoire, Mélina Arguin, Marc-André Brazeau, Frédéric Leduc, Isabelle Marois, Martin V Richter, Guylain Boissonneault
RÉSUMÉ

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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