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Nuclear localization of the glutaminyl-tRNA synthetase QARS reveals its role in DNA damage response in ovarian cancer.

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Τίτλος: Nuclear localization of the glutaminyl-tRNA synthetase QARS reveals its role in DNA damage response in ovarian cancer.
Συγγραφείς: Serafini M; Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris, France.; Inserm U1339, CNRS UMR3666, 26 rue d'Ulm, Paris, France., Di Fazio F; Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris, France.; Inserm U1339, CNRS UMR3666, 26 rue d'Ulm, Paris, France.; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Kieffer Y; Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris, France.; Inserm U1339, CNRS UMR3666, 26 rue d'Ulm, Paris, France., Djerroudi L; Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris, France.; Inserm U1339, CNRS UMR3666, 26 rue d'Ulm, Paris, France.; Institut Curie, Department of Diagnostic and Theranostic Medicine, PSL Research University, 26, rue d'Ulm, Paris, France., Dec L; Institut Curie, PSL Research University, CurieCoreTech Mass Spectrometry Proteomics, Paris, France., Richard M; Institut Curie, PSL Research University, CurieCoreTech Mass Spectrometry Proteomics, Paris, France., Aubert Y; University of Toulouse, Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), Inserm UMR1291, CNRS UMR5051, CHU Purpan, Toulouse, France., Marchesoni-Acland F; Université Paris-Saclay, ENS Paris-Saclay, CNRS UMR9010, Centre Borelli, Gif-sur-Yvette, France., Diaz-Munoz MD; University of Toulouse, Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), Inserm UMR1291, CNRS UMR5051, CHU Purpan, Toulouse, France., Vincent-Salomon A; Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris, France.; Inserm U1339, CNRS UMR3666, 26 rue d'Ulm, Paris, France.; Institut Curie, Department of Diagnostic and Theranostic Medicine, PSL Research University, 26, rue d'Ulm, Paris, France., Vagner S; Institut Curie, PSL Research University, CNRS UMR3348, Inserm, Orsay, France., Loew D; Institut Curie, PSL Research University, CurieCoreTech Mass Spectrometry Proteomics, Paris, France., Ceccaldi R; Inserm U1339, CNRS UMR3666, 26 rue d'Ulm, Paris, France.; Alternative DNA repair mechanisms in human cancers, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris, France., Mechta-Grigoriou F; Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris, France. fatima.mechta-grigoriou@curie.fr.; Inserm U1339, CNRS UMR3666, 26 rue d'Ulm, Paris, France. fatima.mechta-grigoriou@curie.fr., Mieulet V; Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris, France. virginie.mieulet@inserm.fr.; Inserm U1339, CNRS UMR3666, 26 rue d'Ulm, Paris, France. virginie.mieulet@inserm.fr.; University of Toulouse, Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), Inserm UMR1291, CNRS UMR5051, CHU Purpan, Toulouse, France. virginie.mieulet@inserm.fr.
Πηγή: Nature communications [Nat Commun] 2026 Aug 07; Vol. 17 (1). Date of Electronic Publication: 2026 Aug 07.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Imprint Name(s): Original Publication: [London] : Nature Pub. Group
Ιατρικοί όροι (MeSH): Ovarian Neoplasms*/genetics , Ovarian Neoplasms*/pathology , Ovarian Neoplasms*/metabolism , Ovarian Neoplasms*/enzymology , Cell Nucleus*/metabolism , Amino Acyl-tRNA Synthetases*/metabolism , Amino Acyl-tRNA Synthetases*/genetics , DNA Damage*, Autoantigens/metabolism ; Antigens, Nuclear/metabolism ; Chromatin/metabolism ; Humans ; Female ; DNA Repair ; Cell Line, Tumor ; Homologous Recombination ; MRE11 Homologue Protein
Περίληψη: Uncovering novel mechanisms controlling DNA damage response (DDR) is essential to better understand the molecular features of high-grade serous ovarian cancers (HGSOC), which remain a clinical challenge. Here, we demonstrate that the glutaminyl-tRNA-synthetase QARS is a key player in DDR. We show that QARS is regulated at translational level by the MAPK pathway in HGSOC and controls homologous recombination (HR) through a translation-independent mechanism. Analyses combining RNA sequencing, immunohistochemistry, proteomic data and functional assays from HGSOC patient cohorts and relevant cellular models reveal that QARS promotes DNA repair via the HR pathway. Interestingly, we uncover that QARS is located in the nucleus and is enriched at chromatin upon DNA damage. Nuclear QARS controls HR by interacting with the nuclear autoantigen SP100, a major component of PML-nuclear bodies (PML-NB), that are regulatory hubs for DNA repair proteins. Our data highlight nuclear functions and mechanisms for QARS involving SP100, PML-NB and MRE11 that enhance HR in HGSOC.
(© 2026. The Author(s).)
Competing Interests: Competing interests: F.M.-G. received research support from Roche and Institut Roche. The remaining authors declare no competing interests.
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Substance Nomenclature: EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
0 (Autoantigens)
0 (Antigens, Nuclear)
0 (MRE11 protein, human)
0 (Chromatin)
EC 3.1.- (MRE11 Homologue Protein)
Entry Date(s): Date Created: 20260907 Date Completed: 20260907 Latest Revision: 20260910
Update Code: 20260910
PubMed Central ID: PMC13550464
DOI: 10.1038/s41467-026-76046-w
PMID: 42706241
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2041-1723
DOI:10.1038/s41467-026-76046-w