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Le facteur de réparation XPC est un cofacteur de l'ARN polymérase II régulant les modifications post-traductionnelles des histones lors de la transcription

Abstract : NER involves a cascade of protein complexes including the DNA damage sensor (XPC/HR23B). Mutations in NER genes (TTD-A, XPA-G, XPV, CSA and CSB) are associated with human genetic diseases including Xeroderma pigmentosum (XP), Trichothiodystrophy (TTD) and Cockayne Syndrome (CS). All the symptoms can only be explained by a defect of the DNA repair. However all the symptoms can only be explained by a defect of the DNA repair. However, it has been proven that NER factors are also involved in transcription. As the genomic scale to better understand the consequences of its deregulation in a pathological context. In this sense, my second goal has been to characterize at the molecular level the etiology of new XP patients by analyzing in a combined way the molecular events of the NER and the transcription associated with XPC. Our different experimental approaches have made it possible to identify at genomic level a set of gene whose promoters are regulated both positively and negatively by XPC in a dependent RAR context. In addition, we show that XPC interacts with KAT2A contained in the ATAC complex, as well as with the transcription factor E2F1, the chromatin remodeling factor BRD2, and the histone variant H2A.Z. Via KAT2A, this complex will acetylate not only H2A.Z but also H3K9 at promoters targeted by E2F1.
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Maryssa Semer. Le facteur de réparation XPC est un cofacteur de l'ARN polymérase II régulant les modifications post-traductionnelles des histones lors de la transcription. Génomique, Transcriptomique et Protéomique [q-bio.GN]. Université de Strasbourg, 2018. Français. ⟨NNT : 2018STRAJ040⟩. ⟨tel-02119090⟩

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