Relocation of rDNA repeats for repair is dependent on SUMO-mediated nucleolar release by the Cdc48/p97 segregase
AbstractRibosomal RNA genes (rDNA) are highly unstable and susceptible to rearrangement due to active transcription and their repetitive nature. Compartmentalization of rDNA in the nucleolus suppresses uncontrolled recombination. However, broken repeats must be released to the nucleoplasm to allow repair by homologous recombination. The process of rDNA relocation is conserved from yeast to humans, but the underlying molecular mechanisms are currently unknown. Here we show that DNA damage induces phosphorylation of the CLIP component Nur1, releasing nuclear membrane-tethered rDNA repeats from the nucleolus in Saccharomyces cerevisiae. Cooperating with Nur1 phosphorylation, SUMOylation targets the rDNA tethering complex for disassembly mediated by the segregase Cdc48/p97, which recognizes SUMOylated CLIP-cohibin through its cofactor, Ufd1. Consistent with the conservation of this mechanism, UFD1L depletion impairs rDNA release in human cells. The dynamic and regulated assembly and disassembly of the CLIP-cohibin complex is therefore a key, conserved determinant of nucleolar rDNA release and genome integrity.