期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 55, 期 46, 页码 14244-14247出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201607380
关键词
cisplatin; DNA damage; DNA structures; high-throughput sequencing; medicinal chemistry
资金
- National Basic Research Foundation of China [2016YFC0900301]
- National Natural Science Foundation of China [21472009, 21522201]
- US National Institutes of Health [R01 HG006827]
- Howard Hughes Medical Institute
- Beijing Advanced Innovation Centre for Genomics at Peking University
Cisplatin, one of the most widely used anticancer drugs, crosslinks DNA and ultimately induces cell death. However, the genomic pattern of cisplatin-DNA adducts has remained unknown owing to the lack of a reliable and sensitive genome-wide method. Herein we present cisplatin-seq to identify genome-wide cisplatin crosslinking sites at base resolution. Cisplatin-seq reveals that mitochondrial DNA is a preferred target of cisplatin. For nuclear genomes, cisplatin-DNA adducts are enriched within promoters and regions harboring transcription termination sites. While the density of GG dinucleotides determines the initial crosslinking of cisplatin, binding of proteins to the genome largely contributes to the accumulative pattern of cisplatin-DNA adducts.
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