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

Abstract 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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c4f9f089fbaf4a23a3f257a7acb65763
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spelling	oai:doaj.org-article:c4f9f089fbaf4a23a3f257a7acb657632021-12-02T15:05:56ZChronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways10.1038/s41598-017-04223-52045-2322https://doaj.org/article/c4f9f089fbaf4a23a3f257a7acb657632017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04223-5https://doaj.org/toc/2045-2322Abstract 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.Wen-Pin SuYen-Chih HoCheng-Kuei WuSen-Huei HsuJia-Lin ShiuJheng-Cheng HuangSong-Bin ChangWen-Tai ChiuJan-Jong HungTsung-Lin LiuWei-Sheng WuPei-Yu WuWu-Chou SuJang-Yang ChangHungjiun LiawNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Chronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways
description	Abstract 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.
format	article
author	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
author_facet	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
author_sort	Wen-Pin Su
title	Chronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways
title_short	Chronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways
title_full	Chronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways
title_fullStr	Chronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways
title_full_unstemmed	Chronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways
title_sort	chronic treatment with cisplatin induces chemoresistance through the tip60-mediated fanconi anemia and homologous recombination repair pathways
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c4f9f089fbaf4a23a3f257a7acb65763
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Chronic treatment with cisplatin induces chemoresistance through the TIP60-mediated Fanconi anemia and homologous recombination repair pathways

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