title: 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.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
authors.forename: Xushen
authors.initials: X
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. chuanhe@uchicago.edu.|Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, 100871, China. chuanhe@uchicago.edu.
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China. chengqi.yi@pku.edu.cn.
authors.forename: Chengqi
authors.initials: C
authors.lastname: Yi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D047369:Chromatin Immunoprecipitation; D002945:Cisplatin / Q000032:analysis / Q000737:chemistry*; D018736:DNA Adducts / Q000032:analysis*; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000737:chemistry*; D015894:Genome, Human; D024243:HMGB1 Protein / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D017422:Sequence Analysis, DNA
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D004272:DNA, Mitochondrial; D024243:HMGB1 Protein; C057270:cisplatin-DNA adduct; D002945:Cisplatin
keywords: DNA damage; DNA structures; cisplatin; high-throughput sequencing; medicinal chemistry