Nucleolar Reorganization in Response to RDNA Damage

Nucleoli, sites of ribosome biogenesis, form around nucleolar organizer regions (NORs) comprising rDNA arrays, located on human acrocentric chromosome p-arms. NORs provide an opportunity to investigate the DNA double strand break (DSB) response at highly transcribed, repetitive, essential loci. Targeted introduction of DSBs into rDNA results in ATM-dependent inhibition of RNA-polymerase I transcription, coupled with movement of rDNA from the nucleolar interior to anchoring points at the periphery. Reorganization renders rDNA accessible to repair factors, normally excluded from nucleoli. Importantly, rDNA DSBs recruit the accurate homologous recombination (HR) repair machinery throughout the cell cycle, suggesting that HR can be templated in cis. We discuss recent findings regarding the biophysical properties of nucleoli and suggest a mechanism for stress-induced nucleolar reorganization.