A04
Role of premature transcription termination in colorectal tumorigenesis
Project Summary
In physiological conditions, and primarily in MYC-driven cancer cells, RNA polymerase II encounters different obstacles during gene transcription. These include transcription-replication conflicts, torsional stress, R-loops and replication stress, and can result in RNA polymerase II staling and genomic stability, for example by collisions of the transcription machinery with the replication fork. Our previous work demonstrated that MYC and R-loop-interacting ubiquitin E3 ligases play a role in protecting cancer cells from deleterious effects of transcription stress. In this project, we will use our combined expertise in quantitative proteomics, DNA damage response and cancer biology to gain mechanistic understanding of how the ubiquitin proteasome system enables colorectal cancer cells to cope with transcription stress.
