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

English version

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

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