In TFIIH the Arch domain of XPD is mechanistically essential for transcription and DNA repair
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-229857
- The XPD helicase is a central component of the general transcription factor TFIIH which plays major roles in transcription and nucleotide excision repair (NER). Here we present the high-resolution crystal structure of the Arch domain of XPD with its interaction partner MAT1, a central component of the CDK activating kinase complex. The analysis of the interface led to the identification of amino acid residues that are crucial for the MAT1-XPD interaction. More importantly, mutagenesis of the Arch domain revealed that these residues areThe XPD helicase is a central component of the general transcription factor TFIIH which plays major roles in transcription and nucleotide excision repair (NER). Here we present the high-resolution crystal structure of the Arch domain of XPD with its interaction partner MAT1, a central component of the CDK activating kinase complex. The analysis of the interface led to the identification of amino acid residues that are crucial for the MAT1-XPD interaction. More importantly, mutagenesis of the Arch domain revealed that these residues are essential for the regulation of (i) NER activity by either impairing XPD helicase activity or the interaction of XPD with XPG; (ii) the phosphorylation of the RNA polymerase II and RNA synthesis. Our results reveal how MAT1 shields these functionally important residues thereby providing insights into how XPD is regulated by MAT1 and defining the Arch domain as a major mechanistic player within the XPD scaffold.…
Autor(en): | Stefan Peissert, Florian Sauer, Daniel B. Grabarczyk, Cathy Braun, Gudrun Sander, Arnaud PoterszmanORCiD, Jean-Marc Egly, Jochen Kuper, Caroline Kisker |
---|---|
URN: | urn:nbn:de:bvb:20-opus-229857 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Medizinische Klinik und Poliklinik II |
Fakultät für Biologie / Rudolf-Virchow-Zentrum | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Nature Communications |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 11 |
Heft / Ausgabe: | 1 |
Aufsatznummer: | 1667 |
Originalveröffentlichung / Quelle: | Nature Communications 11, 1667 (2020). https://doi.org/10.1038/s41467-020-15241-9 |
DOI: | https://doi.org/10.1038/s41467-020-15241-9 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Freie Schlagwort(e): | binding; fluorescence; helicase; kinease; nuclear receptors; nucleotide excision repair; recognition; subunit; sulfur; transactivation |
Datum der Freischaltung: | 16.04.2021 |
Sammlungen: | Open-Access-Publikationsfonds / Förderzeitraum 2020 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |