TY  - JOUR
A1  - Radu, Laura
A1  - Schoenwetter, Elisabeth
A1  - Braun, Cathy
A1  - Marcoux, Julien
A1  - Koelmel, Wolfgang
A1  - Schmitt, Dominik R.
A1  - Kuper, Jochen
A1  - Cianférani, Sarah
A1  - Egly, Jean M.
A1  - Poterszman, Arnaud
A1  - Kisker, Caroline
T1  - The intricate network between the p34 and p44 subunits is central to the activity of the transcription/DNA repair factor TFIIH
T2  - Nucleic Acids Research
N2  - 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.
KW  - general transcription factor IIH (TFIIH)
KW  - DNA repair
KW  - protein–protein interaction
KW  - p44
KW  - p34
Y1  - 2017
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/17017
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-170173
VL  - 45
IS  - 18
ER  -