The segregation of damaged rDNA from active nucleoli, facilitated by the formation of PML-nucleolar compartments (PNAs), can impact several cellular processes and pathways. One major consequence is the disruption of ribosomal RNA synthesis, which is essential for protein production and cell growth. The inhibition of RNA polymerase I (RNAPI) due to the presence of PNAs can lead to nucleolar stress and activation of stress response pathways such as the p53 pathway. Additionally, the segregation of damaged rDNA can affect nucleolar functions beyond ribosome biogenesis, including the regulation of cell cycle progression, DNA repair processes, and cellular signaling pathways. The altered nucleolar dynamics resulting from damaged rDNA segregation can have widespread effects on cellular homeostasis and function.