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Chemical profiling of the genome with anti-cancer drugs defines target specificities

ABSTRACT: Many anti-cancer drugs induce DNA breaks to eliminate tumor cells. The anthracycline topoisomerase II inhibitors can also evict histones. We performed a genome-wide high-resolution mapping of chemotherapeutic effects of various topoisomerase I and II inhibitors. We show that different drugs target different types of chromatin for induction of DNA damage and histone eviction. Topoisomerase inhibitors topotecan and etoposide similarly target transcriptionally active chromatin for DNA damage. Daunorubicin induces DNA breaks and evicts histones in active chromatin, thus quenching local DNA damage response. The analog aclarubicin evicts histones in H3K27me3-marked heterochromatin. These results can guide rational treatment decisions regarding these genome manipulating anti-cancer drugs. FAIRE-seq and g-H2AX ChIP-seq were performed on K562 cells after drug exposure

ORGANISM(S): Homo sapiens  

SUBMITTER: Johann de Jong  Jacques Neefjes   Arno Velds   Baoxu Pang   Ron Kerkhoven   Xiaohang Qiao   Lodewyk F Wessels    

PROVIDER: E-GEOD-60395 | ArrayExpress | 2015-05-22



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