Fig. 5.

Functional roles of biomolecular phase separation in transcriptional activation and genome instability in cancer. a Transcription factors such as FOXM1 form phase-separated condensates at SEs regions, where they colocalize with coactivators and RNA Pol II to facilitate robust transcriptional activation. These condensates bring distal enhancer elements into close proximity with target promoters, enhancing the efficiency and specificity of transcriptional initiation. b Noncoding RNAs, including circRNAs and lncRNAs, scaffold LLPS-driven condensates by recruiting RBPs. These RBPs granules can protect transcripts from degradation or post-transcriptionally modulate their stability, thereby reshaping transcriptomic output in cancer cells. c The E3 ubiquitin ligase RNF168 participates in DNA damage repair through SUMO-dependent phase separation. Biomolecular phase separation facilitates the assembly of repair factors at DNA double-strand break sites; however, excessive or dysregulated condensate formation may sequester repair machinery or interfere with chromatin remodeling, ultimately leading to defective DNA repair and genomic instability. d The deacetylase HDAC6 undergoes phase separation upon phosphorylation and forms aberrant condensates that promote chromatin disorganization. These disordered assemblies impair DNA accessibility and genome architecture, contributing to mutational burden and chromosomal rearrangements