Institute: Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany
Two fundamental processes, RNA polymerase II dependent transcription and nucleotide excision DNA repair (NER) are linked by the multi-protein complex TFIIH. This transcription factor consists of a total of ten subunits and we aim to decipher the different functionalities of the individual subunits and their interplay leading to the required enzymatic activities to permit transcription and repair. Our studies show that XPD assumes entirely different functionalities in both processes. For repair the enzymatic activities are essential. In contrast, none of XPDs enzymatic functions are required for transcription and XPD switches from an enzyme to a structural protein merely preserving TFIIH integrity. We thus have shown that the XPD helicase is exclusively devoted to repair processes and could be targeted by drugs without affecting transcription. XPD might therefore represent an excellent surrogate drug target for cancer therapy approaches using DNA damaging agents like cisplatin.