Abstract
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.
Highlights
Cells are continuously exposed to DNA damages which are repaired by different DNA repair pathways according to the nature of the damage
Ribosomal DNA is composed of repeated sequences and is the most transcribed genomic region
Transcription of ribosomal DNA (rDNA) is essential for cellular homeostasis and cell proliferation
Summary
Cells are continuously exposed to DNA damages which are repaired by different DNA repair pathways according to the nature of the damage (double- or single-strand breaks, base modifications,. . .). Cells are continuously exposed to DNA damages which are repaired by different DNA repair pathways according to the nature of the damage DNA double-strand breaks (DSBs) are among the most deleterious DNA damage and cells have developed two main pathways to repair them: homologous recombination (HR) and non-homologous end joining (NHEJ)[1]. We focused on ribosomal DNA (rDNA) the most transcribed genomic locus. It is composed of tandem repeats (200–300) present on the five acrocentric chromosomes in human cells [2]. RDNA localises within specialized subcompartments, the nucleoli, in which rDNA transcription and rRNA processing take place
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