Solution structure and self-association properties of the p8 TFIIH subunit responsible for trichothiodystrophy.

Archive ouverte

Vitorino, Marc | Coin, Frédéric | Zlobinskaya, Olga | Atkinson, Robert Andrew | Moras, Dino | Egly, Jean-Marc | Poterszman, Arnaud | Kieffer, Bruno

Edité par CCSD ; Elsevier -

Trichothiodystrophy (TTD) is a rare hereditary multi-system disorder associated with defects in nucleotide excision repair (NER) and transcription as consequences of mutations in XPB, XPD and p8/TTD-A subunits of transcription factor IIH (TFIIH). Here, we report the solution structure of the p8/TTD-A protein, a small alpha/beta protein built around an antiparallel beta-sheet that forms a homodimer with an extended interface. In order to characterize the dimer interface, we have introduced a mutation at position 44, which destabilizes the dimeric form of the protein. We have shown that this mutation has no effect on the intrinsic ability of p8/TTD-A to stimulate NER in vitro, but affects the capacity of p8/TTD-A to restore TFIIH concentration in TTD-A fibroblasts. Point mutations found in TTD-A patients are discussed on the basis of the present structure.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion