Chronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways

Wen Pin Su, Yen Chih Ho, Cheng Kuei Wu, Sen Huei Hsu, Jia Lin Shiu, Jheng Cheng Huang, Song Bin Chang, Wen Tai Chiu, Jan Jong Hung, Tsung Lin Liu, Wei Sheng Wu, Pei Yu Wu, Wu Chou Su, Jang Yang Chang, Hungjiun Liaw

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14 引文 斯高帕斯(Scopus)

摘要

The Fanconi anemia pathway in coordination with homologous recombination is essential to repair interstrand crosslinks (ICLs) caused by cisplatin. TIP60 belongs to the MYST family of acetyltransferases and is involved in DNA repair and regulation of gene transcription. Although the physical interaction between the TIP60 and FANCD2 proteins has been identified that is critical for ICL repair, it is still elusive whether TIP60 regulates the expression of FA and HR genes. In this study, we found that the chemoresistant nasopharyngeal carcinoma cells, derived from chronic treatment of cisplatin, show elevated expression of TIP60. Furthermore, TIP60 binds to the promoters of FANCD2 and BRCA1 by using the chromatin immunoprecipitation experiments and promote the expression of FANCD2 and BRCA1. Importantly, the depletion of TIP60 significantly reduces sister chromatid exchange, a measurement of HR efficiency. The similar results were also shown in the FNACD2-, and BRCA1-deficient cells. Additionally, these TIP60-deficient cells encounter more frequent stalled forks, as well as more DNA double-strand breaks resulting from the collapse of stalled forks. Taken together, our results suggest that TIP60 promotes the expression of FA and HR genes that are important for ICL repair and the chemoresistant phenotype under chronic treatment with cisplatin.
原文英語
文章編號3879
期刊Scientific Reports
7
發行號1
DOIs
出版狀態已發佈 - 12月 2017
對外發佈

ASJC Scopus subject areas

  • 多學科

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