PT  - JOURNAL ARTICLE
AU  - Matías Capella
AU  - Imke K. Mandemaker
AU  - Fabian den Brave
AU  - Lucía Martín Caballero
AU  - Boris Pfander
AU  - Andreas G. Ladurner
AU  - Stefan Jentsch
AU  - Sigurd Braun
TI  - Relocation of rDNA repeats for repair is dependent on SUMO-mediated nucleolar release by the Cdc48/p97 segregase
AID  - 10.1101/2021.01.05.425376
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.05.425376
4099  - http://biorxiv.org/content/early/2021/01/20/2021.01.05.425376.short
4100  - http://biorxiv.org/content/early/2021/01/20/2021.01.05.425376.full
AB  - Ribosomal 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-cohibin complex, releasing membrane-tethered rDNA from the nucleolus in Saccharomyces cerevisiae. Downstream of phosphorylation, SUMOylation targets CLIP-cohibin for disassembly mediated by the Cdc48/p97 chaperone, which recognizes SUMOylated CLIP-cohibin through its cofactor, Ufd1. Consistent with a conserved mechanism, UFD1L depletion impairs rDNA release in human cells. The dynamic and regulated assembly and disassembly of the rDNA-tethering complex is therefore a key determinant of nucleolar rDNA release and genome integrity.Competing Interest StatementThe authors have declared no competing interest.