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

Autor: Fages J; LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France., Chailleux C; LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France., Humbert J; Centre de Recherche sur le Cancer de l'Université Laval, axe Oncologie du Centre de recherche du CHU de Québec-Université Laval, Québec, Canada., Jang SM; Centre de Recherche sur le Cancer de l'Université Laval, axe Oncologie du Centre de recherche du CHU de Québec-Université Laval, Québec, Canada., Loehr J; 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., Lambert JP; 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., Côté J; Centre de Recherche sur le Cancer de l'Université Laval, axe Oncologie du Centre de recherche du CHU de Québec-Université Laval, Québec, Canada., Trouche D; LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France., Canitrot Y; LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2020 Jun 29; Vol. 16 (6), pp. e1008511. Date of Electronic Publication: 2020 Jun 29 (Print Publication: 2020).
DOI: 10.1371/journal.pgen.1008511
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje