Phase Separation Modulates the Formation and Stabilities of DNA Guanine Quadruplex.
Zi GaoJun YuanXiaomei HeHanding WangYinsheng WangPublished in: JACS Au (2023)
In the presence of monovalent alkali metal ions, G-rich DNA sequences containing four runs of contiguous guanines can fold into G-quadruplex (G4) structures. Recent studies showed that these structures are located in critical regions of the human genome and assume important functions in many essential DNA metabolic processes, including replication, transcription, and repair. However, not all potential G4-forming sequences are actually folded into G4 structures in cells, where G4 structures are known to be dynamic and modulated by G4-binding proteins as well as helicases. It remains unclear whether there are other factors influencing the formation and stability of G4 structures in cells. Herein, we showed that DNA G4s can undergo phase separation in vitro . In addition, immunofluorescence microscopy and ChIP-seq experiments with the use of BG4, a G4 structure-specific antibody, revealed that disruption of phase separation could result in global destabilization of G4 structures in cells. Together, our work revealed phase separation as a new determinant in modulating the formation and stability of G4 structures in human cells.
Keyphrases
- high resolution
- induced apoptosis
- single molecule
- circulating tumor
- cell cycle arrest
- cell free
- single cell
- signaling pathway
- transcription factor
- genome wide
- endoplasmic reticulum stress
- gene expression
- endothelial cells
- oxidative stress
- circulating tumor cells
- dna methylation
- risk assessment
- optical coherence tomography
- mass spectrometry
- rna seq
- climate change
- pi k akt
- high speed
- induced pluripotent stem cells