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Base‐Resolution Analysis of Cisplatin–DNA Adducts at the Genome Scale
Author(s) -
Shu Xiaoting,
Xiong Xushen,
Song Jinghui,
He Chuan,
Yi Chengqi
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201607380
Subject(s) - cisplatin , genome , dna , mitochondrial dna , dna damage , adduct , base pair , chemistry , biology , microbiology and biotechnology , genetics , gene , organic chemistry , chemotherapy
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.