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Using Pt-seq, we identified tens to hundreds of binding clusters that are 10 to 20\u00a0kilobases in median length and highly consistent among different drugs, predominantly localizing to centromeric and ribosomal DNA regions. In cisplatin-resistant cells, we found significantly reduced binding within these regions. Moreover, we found that mutations in cancer cells can generate previously unidentified binding sites. On this basis, we demonstrated that ICR-191, an acridine orange compound capable of inducing G insertions, enhances cisplatin-DNA binding and sensitizes cells to cisplatin. Collectively, Pt-seq sensitively profiles Pt\u2013DNA interactions and deepens our understanding of the genome-wide effect of chemotherapeutic drugs.<\/jats:p>","DOI":"10.1126\/sciadv.adx6809","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:58:36Z","timestamp":1761760716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Pt-seq unveils the genomic binding pattern of platinum-based drugs"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0443-378X","authenticated-orcid":true,"given":"Chuyun","family":"Shao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Peking University, Beijing, China."},{"name":"Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 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