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A screen in isogenic cells revealed that KRAS activation positively modulates STN1 expression, a component of the CTC1\u2013STN1\u2013TEN1 (CST) complex. We find that STN1 is significantly upregulated in PC and its elevation is correlated with KRAS oncogenic mutations, while inhibition of KRAS signaling decreases STN1 expression. Interestingly, depletion of STN1 increases DNA damage and\u00a0replication stress, and sensitizes PC cells to ionizing radiation independent of CTC1 and TEN1. STN1 silencing reduces both homologous recombination and non-homologous end joining repair of double-strand breaks (DSBs), suggesting STN1 ensures proper DSB repair. Furthermore, knockdown of STN1 impairs cell cycle arrest at G2\/M phase in response to ionizing radiation, which is accompanied by increased mitotic catastrophe. Proteomic analysis reveals that STN1 physically interacts with proteins important for DNA repair, replication, and cell cycle progression, including ATM, DICER, CEP164, and CEP250. In particular, STN1 appears to stabilize ATM expression and promote proper ATM signaling after DNA damage. Our findings have revealed a novel CST complex-independent role of STN1 in DSB repair and suggest\u00a0STN1 may be a promising target for cancer therapy.<\/jats:p>","DOI":"10.1093\/nar\/gkaf983","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T08:58:30Z","timestamp":1759395510000},"source":"Crossref","is-referenced-by-count":4,"title":["KRAS-induced STN1 (OBFC1) promotes proper CTC1\u2013STN1\u2013TEN1\u00a0complex-independent DNA double-strand break repair and cell cycle checkpoint maintenance in pancreatic cancer"],"prefix":"10.1093","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7668-7166","authenticated-orcid":false,"given":"Changxian","family":"Shen","sequence":"first","affiliation":[{"name":"City of Hope National Medical Center Department of Radiation Oncology, , Duarte, 91010 ,","place":["United 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Center Department of Radiation Oncology, , Duarte, 91010 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindhu","family":"Nair","sequence":"additional","affiliation":[{"name":"City of Hope National Medical Center Department of Radiation Oncology, , Duarte, 91010 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Li","sequence":"additional","affiliation":[{"name":"Integrative Genomic Core, Beckman Research Institute of City of Hope , Duarte, 91010 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna M","family":"Karasinska","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC, BC Cancer Research Centre , Vancouver , BC, V5Z 0B4 ,\u00a0","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T","family":"Topham","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC, BC Cancer Research Centre , Vancouver , BC, V5Z 0B4 ,\u00a0","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Renouf","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC, BC Cancer Research Centre , Vancouver , BC, V5Z 0B4 ,\u00a0","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u00a0F","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC, BC Cancer Research Centre , Vancouver , BC, V5Z 0B4 ,\u00a0","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Beckman Research Institute of the\u00a0City of Hope Department of Cancer Genetics and Epigenetics, , Duarte, 91010 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Ping","sequence":"additional","affiliation":[{"name":"Beckman Research 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