Julio, L. R. | Search bioRxiv

bioRxiv2026

G4 DNA structures induced by UV radiation: a multi-omic approach

DNA G quadruplexes (G4s) are secondary structures with critical roles in regulating genome function. G4s in regulatory regions like promoters and enhancers are important for controlling gene expression, while aberrant formation of G4s has been linked to genomic instability and human disease. Despite G4s importance and inherent danger, their dynamic formation remains incompletely understood. Here, we show that ultraviolet (UV) radiation uniquely induces widespread and persistent G4 formation in human cells, distinguishing it from other genotoxins. Through integrated genomic, transcriptomic, and proteomic analyses, we uncovered key features and functions of UV-induced G4s. Proteomic profiling identified RCOR3 as a factor associated with specific UV-induced G4s at late time points. Functional studies revealed that RCOR3 is essential for the formation and persistence of these structures. Furthermore, genes associated with UV G4s that are differentially expressed are enriched in pathways related to response to UV radiation, highlighting their biological relevance. These findings define the multi-omic landscape of UV-induced G4s and reveal new mechanistic insights into the interplay between genotoxic stress responses and the regulation of non-canonical DNA structures. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/738736v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@8c2e32org.highwire.dtl.DTLVardef@12d1379org.highwire.dtl.DTLVardef@5971a3org.highwire.dtl.DTLVardef@33bcee_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

The Role of BAZ2-dependent Chromatin Remodeling in Suppressing G4 DNA Structures and Associated Genomic Instability

DNA G-quadruplexes (G4s) are secondary structures with significant roles in regulating genome function and stability. Dysregulation of the dynamic formation of G4s is linked to genomic instability and disease, but the underlying mechanisms are not fully understood. In this study, we conducted a screen of chromatin-modifying enzymes and identified nine potential inhibitors of G4 formation, including seven that were not previously characterized. Among these, we highlight the role of BAZ2 chromatin remodelers as key suppressors of G4 DNA and G4-related genome instability. Depletion of BAZ2 subunits led to increased G4 formation, especially at transcriptional regulatory elements. BAZ2B was found to associate with G4 loci, suggesting that it plays a direct role in suppressing G4s. While BAZ2-deficient cells exhibited modest genomic instability, treatment with the G4-stabilizing ligand BRACO19 exacerbated double-strand breaks (DSBs), highlighting its utility as a tool to study G4-dependent genome instability. DSB profiling using INDUCE-seq uncovered distinct breakage patterns around G4s, further underscoring the impact of G4s on genome integrity. Notably, we found that within G4s, G repeats were more susceptible to DSBs than loops. These results establish BAZ2 chromatin remodeling complexes as direct regulators of G4 dynamics and provide new insights into G4-dependent genome instability.

molecular biology↗