Pt-seq unveils the genomic binding pattern of platinum-based drugs [Pt-seq]
Platinum-based drugs (Pt drugs) are widely used in cancer chemotherapy, yet their genome-wide DNA binding patterns remain incompletely understood. Here, we present Pt-seq, an antibody-assisted, genome-wide method for mapping Pt-DNA adducts at single-base resolution. By employing exo- and endo- nucleases to remove background DNA, Pt-seq enables highly robust and sensitive profiling of binding sites for cisplatin, oxaliplatin, lobaplatin, and a Pt(IV) complex. Using Pt-seq, we identified hundreds to a few thousand binding clusters that are 10-20 kb in length and highly consistent among different Pt drugs. Notably, these binding clusters predominantly localize to centromeric and rDNA regions. In cisplatin-resistant cells, we found significantly reduced binding within these regions, suggesting a potential role in drug resistance. Moreover, we found that de novo mutations in cancer cells can create novel binding sites for Pt drugs. Based on this, we demonstrated that ICR-191, an acridine orange compound capable of inducing G insertions, enhances cisplatin-DNA crosslinking and sensitizes cells to Pt drugs. Collectively, Pt-seq sensitively profiles Pt drug-DNA interactions and deepens our understanding of the genome-wide effect of chemotherapeutic drugs. Overall design: This dataset includes Pt-drugs treatment on HeLa cells, including cisplatin, oxaliplatin, lobaplatin and Pt-Bio-I, also includes cisplatin treatment on A549 wildtype and cisplatin-resistant cell lines (all Pt-seq libraries). Besides, this dataset includes Pt-seq of cisplatin treatment on CHO cell lines, with or without ICR-191 treatment as well. Target-seq libraries on HGPRT gene of CHO with or without ICR-191 treatment are also included.