{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:51:37Z","timestamp":1787824297641,"version":"build-2784847793"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Multinucleated cells are present in lung tissues of patients infected by SARS\u2010CoV\u20102. Although the spike protein can cause the fusion of infected cells and ACE2\u2010expressing cells to form syncytia and induce damage, how host cell responses to this damage and the role of DNA damage response (DDR) signals in cell fusion are still unclear. Therefore, we investigated the effect of SARS\u2010CoV\u20102 spike protein on the fusion of homologous and heterologous cells expressing ACE2 in vitro models, focusing on the protein levels of ATR and ATM, the major kinases responding to DNA damage, and their substrates CHK1 and CHK2. We found that both homologous and heterologous cell fusion activated the ATR\u2010CHK1 and ATM\u2010CHK2 signaling axis and induced the aggregation of \u03b3H2AX, 53BP1 and RAD51 in syncytia. In addition, siRNA or inhibitors of ATM and ATR suppressed syncytia formation by decreasing the level of S protein. These results showed the important role of DDR in stabilizing the S protein and in favoring its induction of cell fusion and syncytium formation, suggesting that the virus exploits the host DDR to facilitate its spread among infected cells.<\/jats:p>","DOI":"10.1002\/jmv.70137","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T12:31:12Z","timestamp":1735561872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["ATM\/ATR\u2010Mediated DNA Damage Response Facilitates SARS\u2010CoV\u20102 Spike Protein\u2010Induced Syncytium Formation"],"prefix":"10.1002","volume":"97","author":[{"given":"Xiaotong","family":"Zhao","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, State Key Laboratory of Advanced Medical Materials and Devices Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union 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