近日,北京大学使用IPHASE品牌产品:HGPRT 基因突变试剂盒在《Science Advances》权威期刊上发表文章《Pt-seq unveils the genomic binding pattern of platinum-based drugs》,影响因子12.5!
【摘要】
Platinum-based drugs (Pt drugs) are widely used in cancer chemotherapy, yet their genome-wide binding patterns remain incompletely understood. Here, we present Pt sequencing (Pt-seq), an antibody-assisted, genomewide method for mapping Pt-DNA adducts at single-base resolution. By using exo- and endonucleases to remove background, Pt-seq enables robust and sensitive profiling of binding sites for cisplatin, oxaliplatin, lobaplatin, and a Pt(IV) complex. Using Pt-seq, we identified tens to hundreds of binding clusters that are 10 to 20 kilobases 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 cisplatinDNA binding and sensitizes cells to cisplatin. Collectively, Pt-seq sensitively profiles Pt–DNA interactions and deepens our understanding of the genome-wide effect of chemotherapeutic drugs.