JMJD6 participates in the maintenance of ribosomal DNA integrity in response to DNA damage
Autoři:
Jérémie Fages aff001; Catherine Chailleux aff001; Jonathan Humbert aff002; Suk-Min Jang aff002; Jérémy Loehr aff003; Jean-Philippe Lambert aff003; Jacques Côté aff002; Didier Trouche aff001; Yvan Canitrot aff001
Působiště autorů:
LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France
aff001; Centre de Recherche sur le Cancer de l'Université Laval, axe Oncologie du Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
aff002; Centre de Recherche sur le Cancer de l'Université Laval, axe Endocrinologie et néphrologie du Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
aff003
Vyšlo v časopise:
JMJD6 participates in the maintenance of ribosomal DNA integrity in response to DNA damage. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008511
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008511
Souhrn
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.
Klíčová slova:
Cell staining – DNA damage – DNA transcription – Histones – Ionizing radiation – Non-homologous end joining – Small interfering RNAs – Nucleolus
Zdroje
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