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Base-Resolution Analysis of Cisplatin-DNA Adducts at the Genome Scale.

ABSTRACT: 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.

SUBMITTER: Shu X

PROVIDER: S-EPMC5131569 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Base-Resolution Analysis of Cisplatin-DNA Adducts at the Genome Scale.

Shu Xiaoting X Xiong Xushen X Song Jinghui J He Chuan C Yi Chengqi C

Angewandte Chemie (International ed. in English) 20161013 46

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 p ...[more]

PMID: 27736024

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