Abstract 1883 Biomolecular condensate formation, dynamics, and signaling in nucleoli and therapeutic implications in cancers

Cancer cells require more rRNA synthesis and processing in the nucleoli to meet the increased demand for protein synthesis. Ribosomal RNA (rRNA) synthesis by RNA Polymerase I is tightly regulated by the ATM/ATR-mediated DNA damage response (DDR) pathways in cancer cells. However, it remains elusive how the nucleolar DDR pathway is activated and regulated by biomolecular condensates via liquid-liquid phase separation. We have demonstrated that APE1 protein containing a N-terminal intrinsically disordered region (IDR) and a C-terminal nuclease domain can form LLPS in vitro and in the nucleoli of cancer but not normal cells, and that APE1 promotes the nucleolar ATR-mediated DDR activation to regulate rRNA synthesis.