{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:25:05Z","timestamp":1764653105196,"version":"3.46.0"},"reference-count":37,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Science","doi-asserted-by":"publisher","award":["RS-2022-NR070848","RS-2023-NR077256"],"award-info":[{"award-number":["RS-2022-NR070848","RS-2023-NR077256"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>While PARP inhibitors like Olaparib are effective against BRCA1-deficient breast cancers, their efficacy in BRCA1-proficient tumors depends on the functional status of homologous recombination (HR) repair. Here, we identify the structure-specific endonuclease SLX1 as a key regulator of HR and a determinant of Olaparib sensitivity in BRCA1-intact breast cancer. SLX1 is frequently upregulated in breast cancer and associated with poor prognosis. Functional studies revealed that SLX1 promotes RAD51-mediated HR repair of DNA double-strand breaks. Consequently, SLX1 depletion reduces HR efficiency, increases chromosomal instability, and sensitizes breast-proficient breast cancer cells to DNA-damaging agents, including camptothecin, ionizing radiation, and Olaparib. In contrast, SLX1 overexpression enhances DNA repair capacity and promotes Olaparib resistance. In vivo, SLX1 knockdown synergizes with Olaparib to suppress tumor growth in xenograft models. These findings establish SLX1 as a critical regulator of HR function in BRCA1-proficient breast cancer and a promising target for restoring PARP inhibitor sensitivity through induced HR deficiency.<\/jats:p>","DOI":"10.3390\/ijms262311621","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:13:49Z","timestamp":1764576829000},"page":"11621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SLX1 Inhibition Enhances Olaparib Sensitivity by Impairing Homologous Recombination Repair in Breast Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Jin-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Laboratory of Genomic Instability and Cancer Therapeutics, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"},{"name":"Department of Cellular and Molecular Medicine, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeeho","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Instability and Cancer Therapeutics, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"},{"name":"Department of Pharmacology, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In-Youb","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Gon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Hemato-Oncology, Chosun University Hospital Internal Medicine, Gwangju 61453, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ho Jin","family":"You","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Instability and Cancer Therapeutics, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"},{"name":"Department of Pharmacology, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5602-3100","authenticated-orcid":false,"given":"Young Jin","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Instability and Cancer Therapeutics, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"},{"name":"Department of Cellular and Molecular Medicine, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020 GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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