Ribosomal DNA (rDNA) is the most transcribed genomic region and contains hundreds of tandem repeats. Maintaining these rDNA repeats as well as the level of rDNA transcription is essential for cellular homeostasis. DNA damages generated in rDNA need to be efficiently and accurately repaired and rDNA repeats instability has been reported in cancer, aging and neurological diseases. Here, we describe that the histone demethylase JMJD6 is rapidly recruited to nucleolar DNA damage and is crucial for the relocalisation of rDNA in nucleolar caps. Yet, JMJD6 is dispensable for rDNA transcription inhibition. Mass spectrometry analysis revealed that JMJD6 interacts with the nucleolar protein Treacle and modulates its interaction with NBS1. Moreover, cells deficient for JMJD6 show increased sensitivity to nucleolar DNA damage as well as loss and rearrangements of rDNA repeats upon irradiation. Altogether our data reveal that rDNA transcription inhibition is uncoupled from rDNA relocalisation into nucleolar caps and that JMJD6 is required for rDNA stability through its role in nucleolar caps formation.

核糖体DNA（rDNA）是转录最频繁的基因组区域，包含数百个串联重复序列。维持这些rDNA重复序列以及rDNA转录水平对于细胞动态平衡至关重要。rDNA中产生的DNA损伤需要被有效，准确地修复，并且据报道在癌症，衰老和神经系统疾病中rDNA重复序列的不稳定性。在这里，我们描述了组蛋白脱甲基酶JMJD6被迅速招募到核仁DNA损伤，对于rDNA在核仁帽中的重新定位至关重要。然而，JMJD6可用于rDNA转录抑制。质谱分析表明，JMJD6与核仁蛋白Treacle相互作用并调节其与NBS1的相互作用。此外，缺乏JMJD6的细胞显示出对核仁DNA损伤的敏感性增加，以及辐射后rDNA重复序列的丢失和重排。总的来说，我们的数据表明，rDNA转录抑制与rDNA重新定位到核仁帽中是不相关的，并且JMJD6通过其在核仁帽中的作用来稳定rDNA。