Fig. 3.

Nucleolar response to nuclear or nucleolar DNA damage. DSBs in the nuclear chromatin cause Pol I inhibition in the nucleolus through an ATM-dependent signaling pathway, which includes NBS1, PARP, and Treacle. Pol I is also inhibited upon direct rDNA damage in an ATM-NBS1-MDC1-dependent manner. Inhibition of Pol I transcription is most likely responsible for the formation of nucleolar caps and relocalization of damaged rDNA to this structures, which are enriched in HR and NHEJ factors, thus providing an optimal environment for proper rDNA repair. Notably, cap formation was not observed upon nuclear DNA damage is several studies, in spite of Pol I inhibition. DDR and associated Pol I inhibition activate p53 through the impaired ribosome biogenesis checkpoint (IRBC), NMP1, NCL, ARF, ATM, and ATR. Upon genotoxic stress, Cdc14B is released from the nucleolus to the nucleoplasm where it promotes APC/C^Cdh1-dependent Plk1 degradation, triggering a G2-phase cell-cycle checkpoint. Asterisks indicate DSBs