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Implication of oxidative lesions and base excision repair in the tissue selectivity of the somatic instability of CAG repeats in Huntington’s diseease

Abstract : Huntington’s disease (HD) is a neurodegenerative fatal disease caused by the expansion of CAG repeats in the Huntingtin gene. The expansion length is unstable and proportional to the disease severity. The instability affects differently several tissues, among which the striatum that shows a high instability and degenerates, whereas the cerebellum that shows limited instability is spared from the disease. We addressed the role of oxidative lesions and Base Excision Repair (BER) in the tissue-selectivity of the instability in striatum and cerebellum of R6/1 mouse model. Interestingly, we observed a similar level of oxidative lesions at both tissues. Levels and activities of main BER proteins were globally decreased in striatum relative to cerebellum. Moreover we found that repair outcome is dependent upon BER stoichiometries, lesion location and sequence. Our results suggest a poor cooperation between BER activities that could underlie tissue-specificity of somatic instability in HD.
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Submitted on : Tuesday, October 1, 2013 - 5:32:09 PM
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Agathi Vasiliki Goula. Implication of oxidative lesions and base excision repair in the tissue selectivity of the somatic instability of CAG repeats in Huntington’s diseease. Biochemistry, Molecular Biology. Université de Strasbourg, 2012. English. ⟨NNT : 2012STRAJ111⟩. ⟨tel-00868694⟩

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