Previous and current research
During transcript elongation, RNA polymerase II (RNAPII) faces two major obstacles to its progression: chromatin structure and DNA damage. The ability of cells to deal with these challenges is essential for efficient transcription, disease prevention, and survival. To elucidate basic mechanisms of transcriptional elongation, we have isolated the elongating form of RNAPII and found that it is a holoenzyme, consisting of core polymerase and a complex, called Elongator. One of the subunits of Elongator, Elp3, is a histone acetyltransferase, suggesting that the Elongator complex helps RNAPII to transcribe through chromatin. We are presently undertaking a thorough characterisation of the Elongator complex by a combination of biochemical and genetic approaches in both yeast and human cells.

We have also isolated the 'transcription-coupling repair factor', Rad26 (yeast Cockayne's Syndrome B protein). Rad26 is associated with a novel factor, termed Def1. Our present work on the function of the Rad26-Def1 complex is shedding new light on the mechanism of transcription-coupled repair in eukaryotes.

Future projects
With our isolation of Elongator and the Rad26-Def1 complex, we are one step closer to an important immediate goal of our research: reconstitution of transcription-coupled repair, as well as transcription-coupled chromatin remodelling in vitro. We expect that such reconstitution will lead to the identification of a number of new protein factors. Using yeast as a model system, and with immediate use of human cells to verify and extend the initial observations done in the model organism, we aim to achieve a thorough understanding of transcript elongation in eukaryotic cells in general.

In the longer term, our aim is thus to understand the cellular mechanisms that couple transcript elongation to genome integrity. We believe that this research will prove important for understanding basic biological processes that lead to human diseases such as cancer.