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In this study, we determined that the EBV oncoprotein, latent membrane protein 1 (LMP1), perturbs DNA damage response (DDR) signaling, activation of cell cycle checkpoints, and sensitivity to cisplatin in NPC cells (HK1). Hypersensitivity was validated by LMP1 knockdown and CRISPR\/Cas9 targeting in HK1\u2010EBV cells with latent EBV infection. The conserved PxQxT motif (in CTAR1) and Y384 residue (in CTAR2) were required for the hypersensitivity. Inhibition of ATR (VE821 or AZD6738), but not ATM (KU55933 or AZD0156), phenocopied the G1 arrest and hypersensitivity. Attenuation of DDR signaling and hypersensitivity by LMP1 or ATR inhibition was also observed in the C17 NPC cell line with restored stable LMP1 expression. LMP1 expression in NPC tumors is highly variable. Publicly available RNA\u2010sequencing data from microdissected NPC tumors showed that LMP1 expression in the primary tumors was the lowest in cisplatin\u2010treated patients that experienced recurrence. These findings could have clinical significance in stratifying NPC patients such that tumors with limited or variable LMP1 expression might benefit from ATR inhibitor therapy.<\/jats:p>","DOI":"10.1002\/jmv.70407","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T07:00:33Z","timestamp":1747983633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Disruption of ATR Signaling by Epstein\u2013Barr Virus Latent Membrane Protein 1 Sensitizes Nasopharyngeal Carcinoma Cells to Cisplatin"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-1070","authenticated-orcid":false,"given":"Gabriella","family":"Zarkovic","sequence":"first","affiliation":[{"name":"University of Pittsburgh Medical Center (UPMC) Cancer Virology Program Pittsburgh Pennsylvania USA"},{"name":"Department of Microbiology and Molecular Genetics University of Pittsburgh Pittsburgh 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