JMJD6 participates in the maintenance of ribosomal DNA integrity in response to DNA damage

PLoS Genet. 2020 Jun 29;16(6):e1008511. doi: 10.1371/journal.pgen.1008511. eCollection 2020 Jun.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • DNA Damage*
  • HEK293 Cells
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Protein Binding
  • RNA, Ribosomal / genetics*
  • RNA, Ribosomal / metabolism


  • Cell Cycle Proteins
  • NBN protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • RNA, Ribosomal
  • TCOF1 protein, human
  • JMJD6 protein, human
  • Jumonji Domain-Containing Histone Demethylases

Grants and funding