in-cell NMR of DNA G4 - structure and folding

• Applicant: Professor Dr. Harald Schwalbe
• Subject Area: Structural Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 531012774

Guanosine-rich DNA sequences can form non-canonical four-stranded (tetraplex) structures known as G-quadruplexes (G4). G4 are especially enriched in regulatory eukaryotic genomic regions, including gene promoters and telomeres. In-cell imaging studies provided direct evidence for G4 formation in cells. G4 structures have been shown to play a critical role in gene regulation, DNA replication, and telomere maintenance. G4 structures fulfill their regulatory roles in a highly dynamic way: Disturbing their dynamic equilibria is associated with the misregulation of oncogenic transcription levels and chromosomal stability. The coexistence of different conformational states allows G4s to adapt to cellular stress-induced changes in the intracellular environment. Despite numerous efforts to advance the characterization of these structures, these studies remain challenging since their pronounced structural polymorphism and our inability to emulate reliably intracellular environments corresponding to various physiologically relevant cellular states. In this application, the groups of Trantirek (CZ) and Schwalbe (DE) join forces to address these challenges and investigate structures and folding of G4 DNAs by in-cell NMR. The German partner will focus on characterizíng (re)-folding of D4 structures by applying light-induced G4 release to in-cell NMR.

• DFG Programme: Research Grants
• International Connection: Czech Republic
• Cooperation Partner: Professor Dr. Lukas Trantirek, Ph.D.