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：2021年9月30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.
