Mechanisms opposing genomic instability arising from dysregulated G4s and R-loops (12)

• Subject Area: Cell Biology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 393547839

Genomic DNA can adopt secondary DNA structures such as R-loops and G-quadruplexes (G4s) that regu-late DNA replication, transcription and splicing but can also interfere with replication and thus present a cellintrinsic source of genomic instability that may be linked to inflammation and ageing. To identify relevant defence mechanisms, we propose to develop G4 Proximity Proteomics (G4Prox) to map proteins associating with G4s in physiological conditions, upon pathological G4 accumulation and in human stem cells. We will characterise the role of candidate proteins in suppressing G4s and explore whether G4- and R-loop-dependent genomic instability triggers signalling pathways that influence cytoplasmic processes and the inflammatory response.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1361: Regulation of DNA Repair and Genome Stability
• Applicant Institution: Johannes Gutenberg-Universität Mainz
• Project Head: Professorin Dr. Petra Beli