Experimentelles System zur Analyse der co-transkriptionellen R-Loop-Bildung im Kontext von DNA Replikation in Säugetierzellen

• Antragsteller: Dr. Stephan Hamperl
• Subject Area: Allgemeine Genetik und funktionelle Genomforschung
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 236361818

Accurate DNA replication and DNA repair are crucial for the maintenance of genome stability, and it is generally accepted that failures of these processes are major sources of DNA damage in cells. Intriguingly, recent evidence suggests that DNA damage is more likely to occur at genomic loci with high transcriptional activity. Furthermore, loss of certain RNA processing factors in mammalian cells may lead to DNA damage through the increased formation of co-transcriptional RNA-DNA hybrid structures known as R-loops. The molecular mechanism leading to R-loop formation and how these structures affect genome instability is not well understood. This project aims to establish an in vivo system for controlled transcription and replication timing on an episomal plasmid. Thus, it will be possible to evaluate the contribution of these two central nuclear processes on R-loop formation and genome instability. The episomal system may enable the direct identification of plasmid associated proteins involved in R-loop metabolism by a proteomic approach.

• DFG Programme: Forschungsstipendien
• International Connection: USA
• Gastgeberin: Professorin Karlene Cimprich, Ph.D.