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.

中文翻译：

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用于修复的rDNA重复序列的重新定位取决于Cdc48 / p97 segregase的SUMO介导的核仁释放

核糖体RNA基因（rDNA）高度不稳定，由于活跃的转录及其重复性，很容易发生重排。rDNA在核仁中的区室化抑制了不受控制的重组。但是，断裂的重复序列必须释放到核质中，以允许通过同源重组进行修复。rDNA重定位的过程从酵母到人类都是保守的，但是目前尚不清楚潜在的分子机制。在这里，我们显示DNA损伤诱导CLIP-cohibin复合物的磷酸化，从酿酒酵母中的核仁中释放膜束缚的rDNA。磷酸化的下游，SUMOylation靶向CLIP-cohibin由Cdc48 / p97分子伴侣介导的拆卸，该分子通过其辅助因子Ufd1识别SUMO化的CLIP-cohibin。与保守机制一致，UFD1L耗尽会破坏人细胞中的rDNA释放。因此，rDNA束缚复合物的动态和受调节的组装和拆卸是核仁rDNA释放和基因组完整性的关键决定因素。