|Title||Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Yimit, Askar, Ogun Adebali, Aziz Sancar, and Yuchao Jiang|
|Date Published||2019 Jan 18|
|Keywords||Animals, Antineoplastic Agents, Cisplatin, DNA Adducts, DNA Damage, DNA Repair, Epigenomics, Female, Mice, Inbred C57BL, Organ Specificity, Sequence Analysis, RNA, Transcriptome|
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.
|Alternate Journal||Nat Commun|
|Original Publication||Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs.|
|PubMed Central ID||PMC6338751|
|Grant List||P01 CA142538 / CA / NCI NIH HHS / United States |
P30 ES010126 / ES / NIEHS NIH HHS / United States
R01 ES027255 / ES / NIEHS NIH HHS / United States
R35 GM118102 / GM / NIGMS NIH HHS / United States
Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs.