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2021.9.30 Shunichi Takeda教授(深圳大学)学术报告

时间:2021年09月15日 访问次数:17

报告题目:ATM prevents c-Myc overexpression in the mammary epithelium in response to estrogens
报告人Shunichi Takeda 教授 
主持人:李   磊 教授

时   间:2021930日(周四)下午4点
地   点:纳米楼457报告厅
报告人简介:

Educational experience:

1981-1985: Ph.D. (Physiology), Osaka University School of Medicine, Osaka, Japan. mentor: Tasuku Honjo 

1974-1980: B.Med. (Medical Science), Osaka University School of Medicine, Osaka, Japan 

Scientific research and academic work experience : 

2020-present: Distinguished Professor, Shenzhen University, School of Medicine, China 

2019-present: Editorial Board Member, Nucleic Acids Research (NAR) Cancer and DNA Repair 

1998-2020: Professor, Kyoto University, Graduate School of Medicine, Japan 

1995-1998: Associate Professor, Kyoto University, Graduate School of Medicine, Japan 

1988-1995: Scientist, Basel Institute for Immunology, Switzerland 

1986-1988: Research Assistant, Kyoto University, Graduate School of Medicine, Japan 

1985-1986: Research Fellowship, Kyoto University, Graduate School of Medicine, Japan 

1980-1981: Medical Internship (internal medicine) Osaka University, Hospital, Japan  

Research interests:

DNA repair, DNA recombination, Gene therapy, Chemotherapy of cancer, Radiation Biology 

Abstract:

Carriers of mutations in ATM gene are predisposed to breast cancer risk. ATM prevents oncogenesis by activating p53 in every cell; however, much remains unknown about tissue-specific oncogenesis by ATM loss. Here, we report that ATM ensures appropriate transcriptional response to estrogens, the prominent growth factor for breast cancer. The response associates with the active catalysis of topoisomerase II (TOP2), which generates DNA double-strand breaks (DSBs) covalently associated with TOP2 adducts. We revealed that ATM facilitates DSB repair by promoting the removal of TOP2 adducts in G1 cells. Defective repair of TOP2-dependent DSBs changes the activation profile of estrogen-dependent enhancers and transcriptional response of over 1,000 genes to estrogens, demonstrating the crucial role of DSB repair in transcriptional response. The ATM loss causes prolonged overexpression of c-MYC oncogene in mammary epithelial cells after injection of estrogens into mice. In conclusion, ATM suppresses oncogenic effects of estrogens by repairing TOP2-dependent DSBs.