Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs

Askar, Yimit and Adebali, Ogün and Sancar, Aziz and Jiang, Yuchao (2019) Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs. Nature Communicaitons, 10 . ISSN 2041-1723

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Abstract

The platinum-based drug cisplatin is a widely used first-line therapy for several cancers. Cisplatin interacts with DNA mainly in the form of Pt-d(GpG) di-adduct, which stalls cell proliferation and activates DNA damage response. Although cisplatin shows a broad spectrum of anticancer activity, its utility is limited due to acquired drug resistance and toxicity to non-targeted tissues. Here, by integrating genome-wide high-throughput Damage-seq, XR-seq, and RNA-seq approaches, along with publicly available epigenomic data, we systematically study the genome-wide profiles of cisplatin damage formation and excision repair in mouse kidney, liver, lung and spleen. We find different DNA damage and repair spectra across mouse organs, which are associated with tissue-specific transcriptomic and epigenomic profiles. The framework and the multi-omics data we present here constitute an unbiased foundation for understanding the mechanisms of cellular response to cisplatin. Our approach should be applicable for studying drug resistance and for tailoring cancer chemotherapy regimens.
Item Type: Article
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Ogün Adebali
Date Deposited: 11 Feb 2019 11:38
Last Modified: 26 Apr 2022 10:01
URI: https://research.sabanciuniv.edu/id/eprint/36826

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