Role of premature transcription termination in colorectal tumorigenesis (A04)

• Subject Area: Biochemistry ; Gastroenterology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514894665

In physiological conditions, and in particular in cancer cells, RNAPII encounters obstacles, which can cause DNA double strand break formation and induce genomic instability. We have shown that cancer cells engage components of the ubiquitin system such as the HECT-type ubiquitin ligase UBR5 that associates with MYC and R-loops to resolve such problems and limit transcription stress-associated genomic instability. A central element is stress-induced premature transcription termination, which is regulated by specific ubiquitylation events and may constitute a critical dependency of MYC-driven tumors. This project will therefore define ubiquitin-mediated mechanisms that control the response to transcription stress and couple it to premature termination and will use a transplantation model of colorectal cancer liver metastases to investigate whether the growth of colorectal metastatic tumors depends on these mechanisms.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 387: Functionalizing the Ubiquitin System against Cancer - UbiQancer
• Applicant Institution: Technische Universität München (TUM)
• Project Heads: Professorin Dr. Petra Beli; Professor Dr. Martin Eilers