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Structural basis for group A trichothiodystrophy.

Abstract : Patients with the rare neurodevelopmental repair syndrome known as group A trichothiodystrophy (TTD-A) carry mutations in the gene encoding the p8 subunit of the transcription and DNA repair factor TFIIH. Here we describe the crystal structure of a minimal complex between Tfb5, the yeast ortholog of p8, and the C-terminal domain of Tfb2, the yeast p52 subunit of TFIIH. The structure revealed that these two polypeptides adopt the same fold, forming a compact pseudosymmetric heterodimer via a beta-strand addition and coiled coils interactions between terminal alpha-helices. Furthermore, Tfb5 protects a hydrophobic surface in Tfb2 from solvent, providing a rationale for the influence of p8 in the stabilization of p52 and explaining why mutations that weaken p8-p52 interactions lead to a reduced intracellular TFIIH concentration and a defect in nucleotide-excision repair, a common feature of TTD cells.
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Submitted on : Thursday, January 29, 2009 - 4:25:42 PM
Last modification on : Sunday, March 20, 2022 - 9:36:01 AM


  • HAL Id : inserm-00357162, version 1
  • PUBMED : 19172752



Denis E. Kainov, Marc Vitorino, Jean Cavarelli, Arnaud Poterszman, Jean-Marc Egly. Structural basis for group A trichothiodystrophy.. Nature Structural and Molecular Biology, Nature Publishing Group, 2008, 15 (9), pp.980-4. ⟨inserm-00357162⟩



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