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Nuclear localization of glutaminyl-tRNA synthase QARS reveals its role in DNA damage repair in ovarian cancer

ABSTRACT: 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 new key player in DDR. We show that QARS is regulated at translational level by the MAPK pathway in HGSOC and controls DDR 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 homologous recombination (HR)-mediated DNA repair in HGSOC, a function that requires its enzymatic activity. Interestingly, we uncover that QARS is located in the nucleus. Moreover, DNA damage increases QARS protein levels at the chromatin and its interaction with nuclear autoantigen SP100 and Dioxyuridine Triphosphatase DUT, involved in DNA break sensing and DNA integrity. Our data thus highlight a novel nuclear function and mechanism by which QARS enhances DDR in HGSOC.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Vanessa Masson

LAB HEAD: Damarys Loew

PROVIDER: PXD068960 | Pride | 2026-05-18

REPOSITORIES: Pride

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			Action	DRS
	20250512_142727_Martina_Serafini_proteome_quantification_12052025.sne	Other
	20250715_112735_Martina_Serafini_IP_nuclear_quantification_15072025.sne	Other
	PRIDE_Martina_Serafini_MS_180925.xlsx	Xlsx
	VLD2052.raw	Raw
	VLD2053.raw	Raw

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