# Loss of p53 Provokes NF-κB-Dependent Disruption of Nucleolar Cap and Nucleoplasmic Redistribution of Fibrillarin During Nucleolar Stress

## TL;DR

Loss of p53 causes nucleolar changes during chemotherapy, leading to FBL redistribution and G4-related gene regulation.

## Contribution

Identifies a p53-dependent mechanism linking nucleolar disruption to G4-associated transcription via FBL, CK2α, and MAZ.

## Key findings

- Loss of p53 leads to NF-κB-dependent nucleolar cap disruption during doxorubicin treatment.
- Fibrillarin relocates to nucleoplasm and associates with G4 structures in p53-deficient cells.
- FBL redistribution correlates with CK2α and MAZ in G4-associated transcriptional regulation.

## Abstract

Chemotherapeutic agents targeting ribosome biogenesis induce profound reorganization of nucleolar architecture, yet how the tumor suppressor p53 governs these structural responses remains unclear. Here, we show that loss of p53 leads to NF-κB-dependent disappearance of nucleolar caps induced by doxorubicin (DOXO). Under these conditions, fibrillarin (FBL), which is normally confined to the nucleolus, relocates to the nucleoplasm and forms foci that partially associate with G-quadruplex (G4) structures, non-canonical nucleic acid secondary structures enriched at transcriptionally active genomic regions. To examine whether this redistribution is linked to transcriptional changes, we integrated publicly available transcriptomic datasets and identified genes that were upregulated in p53-deficient cells under DOXO treatment and downregulated upon FBL depletion. Given that casein kinase 2 alpha (CK2α) is a nuclear binding partner of FBL, we further analyzed CK2α-dependent gene programs. This analysis revealed that a fraction of FBL-responsive genes overlapped with CK2α-dependent signatures and were enriched for promoter-proximal G4 structures. Among candidate regulators, the G4-binding transcription factor MAZ emerged as a potential mediator linking nucleoplasmic FBL and CK2α to G4-associated transcriptional regulation. Together, our findings identify a mechanism linking loss of p53 to G4-associated transcriptional reprogramming through nucleolar architectural disruption mediated by an FBL–CK2α–MAZ axis during DOXO treatment.