STIM1 translocation to the nucleus protects cells from DNA damage.

Autor:	Sanchez-Lopez I; Department of Biochemistry and Molecular Biology, School of Life Sciences, Universidad de Extremadura, Badajoz 06006, Spain.; Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, Badajoz 06006, Spain., Orantos-Aguilera Y; Department of Biochemistry and Molecular Biology, School of Life Sciences, Universidad de Extremadura, Badajoz 06006, Spain.; Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, Badajoz 06006, Spain., Pozo-Guisado E; Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, Badajoz 06006, Spain.; Department of Cell Biology, School of Medicine, Universidad de Extremadura, Badajoz 06006, Spain., Alvarez-Barrientos A; Bioscience Applied Techniques Facility, Universidad de Extremadura, Badajoz 06006, Spain., Lilla S; CRUK Scotland Institute, Switchback Road, Glasgow G61 1BD, UK., Zanivan S; CRUK Scotland Institute, Switchback Road, Glasgow G61 1BD, UK.; School of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow G61 1QH, UK., Lachaud C; Cancer Research Centre of Marseille, Aix-Marseille Univ, Inserm, CNRS, Institut Paoli Calmettes, CRCM, Marseille, France.; OPALE Carnot Institute, Paris, France., Martin-Romero FJ; Department of Biochemistry and Molecular Biology, School of Life Sciences, Universidad de Extremadura, Badajoz 06006, Spain.; Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, Badajoz 06006, Spain.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Mar 21; Vol. 52 (5), pp. 2389-2415.
DOI:	10.1093/nar/gkae001
Abstrakt:	DNA damage represents a challenge for cells, as this damage must be eliminated to preserve cell viability and the transmission of genetic information. To reduce or eliminate unscheduled chemical modifications in genomic DNA, an extensive signaling network, known as the DNA damage response (DDR) pathway, ensures this repair. In this work, and by means of a proteomic analysis aimed at studying the STIM1 protein interactome, we have found that STIM1 is closely related to the protection from endogenous DNA damage, replicative stress, as well as to the response to interstrand crosslinks (ICLs). Here we show that STIM1 has a nuclear localization signal that mediates its translocation to the nucleus, and that this translocation and the association of STIM1 to chromatin increases in response to mitomycin-C (MMC), an ICL-inducing agent. Consequently, STIM1-deficient cell lines show higher levels of basal DNA damage, replicative stress, and increased sensitivity to MMC. We show that STIM1 normalizes FANCD2 protein levels in the nucleus, which explains the increased sensitivity of STIM1-KO cells to MMC. This study not only unveils a previously unknown nuclear function for the endoplasmic reticulum protein STIM1 but also expands our understanding of the genes involved in DNA repair. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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