Research objectives and content
Eukaryotic cells have evolved a spectrum of mechanisms to cope with DNA damage. A large number of genes encoding proteins involved in the major cellular repair pathway, nucleotide excision repair (NER), have been identified and analyzed. A protein complex, RNA polymerase II transcription factor IIH (TFIIH), has been shown to be involved directly in transcription, DNA repair, and cellcycle regulation. Thus, TFIIH likely represents a main component in the communication of signals from damaged DNA to the transcription and cell-cycle machineries. Therefore, studies of TFIIH function in these processes, and as a molecular switch between them, are crucial for our understanding of the mechanisms cells employ to avoid deleterious DNA damage leading to oncogenic transformation. By combining the power of yeast genetics with molecular techniques and biochemical analyses, I wish to focus my post doctoral training on: Reconstitution of the TFIIH complex from single (recombinant) subunits to define the functional core, and thereby shed light on the specific role(s) of each protein in the complex. And furthermore, characterization of the nucleotide excision repairosome assembly pathway and the conversion of TFIIH from a transcription factor to a repair complex.
Training content (objective, benefit and expected impact)