Fiche publication
Date publication
août 2017
Journal
Nucleic acids research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah
,
Dr EGLY Jean-Marc
,
Dr POTERSZMAN Arnaud
Tous les auteurs :
Radu L, Schoenwetter E, Braun C, Marcoux J, Koelmel W, Schmitt DR, Kuper J, Cianférani S, Egly JM, Poterszman A, Kisker C
Lien Pubmed
Résumé
The general transcription factor IIH (TFIIH) is a multi-protein complex and its 10 subunits are engaged in an intricate protein-protein interaction network critical for the regulation of its transcription and DNA repair activities that are so far little understood on a molecular level. In this study, we focused on the p44 and the p34 subunits, which are central for the structural integrity of core-TFIIH. We solved crystal structures of a complex formed by the p34 N-terminal vWA and p44 C-terminal zinc binding domains from Chaetomium thermophilum and from Homo sapiens. Intriguingly, our functional analyses clearly revealed the presence of a second interface located in the C-terminal zinc binding region of p34, which can rescue a disrupted interaction between the p34 vWA and the p44 RING domain. In addition, we demonstrate that the C-terminal zinc binding domain of p34 assumes a central role with respect to the stability and function of TFIIH. Our data reveal a redundant interaction network within core-TFIIH, which may serve to minimize the susceptibility to mutational impairment. This provides first insights why so far no mutations in the p34 or p44 TFIIH-core subunits have been identified that would lead to the hallmark nucleotide excision repair syndromes xeroderma pigmentosum or trichothiodystrophy.
Mots clés
Chaetomium, enzymology, Fungal Proteins, chemistry, Humans, Models, Molecular, Mutation, Protein Interaction Domains and Motifs, Protein Subunits, chemistry, Transcription Factor TFIIH, chemistry
Référence
Nucleic Acids Res.. 2017 Aug;:
