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NRF2 preserves genomic integrity by facilitating ATR activation and G2 cell cycle arrest

文献类型：期刊论文

作者Sun, Xiaohui1; Wang, Yan1; Ji, Kaihua1; Liu, Yang1; Kong, Yangyang1; Nie, Shasha1; Li, Na1; Hao, Jianxiu1; Xie, Yi2; Xu, Chang1
刊名NUCLEIC ACIDS RESEARCH
出版日期2020-09-18
卷号48期号:16页码:9109-9123
ISSN号0305-1048
DOI10.1093/nar/gkaa631
通讯作者Xu, Chang(xuchang@irm-cams.ac.cn) ; Du, Liqing(dlq@irm-cams.ac.cn) ; Liu, Qiang(liuqiang@irm-cams.ac.cn)
英文摘要Nuclear factor erythroid 2-related factor 2 (NRF2) is a well-characterized transcription factor that protects cells against oxidative and electrophilic stresses. Emerging evidence has suggested that NRF2 protects cells against DNA damage by mechanisms other than antioxidation, yet the mechanism remains poorly understood. Here, we demonstrate that knockout of NRF2 in cells results in hypersensitivity to ionizing radiation (IR) in the presence or absence of reactive oxygen species (ROS). Under ROS scavenging conditions, induction of DNA double-strand breaks (DSBs) increases the NRF2 protein level and recruits NRF2 to DNA damage sites where it interacts with ATR, resulting in activation of the ATR-CHK1-CDC2 signaling pathway. In turn, this leads to G2 cell cycle arrest and the promotion of homologous recombination repair of DSBs, thereby preserving genome stability. The inhibition of NRF2 by brusatol increased the radiosensitivity of tumor cells in xenografts by perturbing ATR and CHK1 activation. Collectively, our results reveal a novel function of NRF2 as an ATR activator in the regulation of the cellular response to DSBs. This shift in perspective should help furnish a more complete understanding of the function of NRF2 and the DNA damage response.
WOS关键词DNA-DAMAGE RESPONSE ; LUNG-CANCER CELLS ; REPAIR PATHWAY ; TRANSCRIPTION FACTOR ; GENE-EXPRESSION ; PHOSPHORYLATION ; KINASE ; RECRUITMENT ; APOPTOSIS ; PROMOTES
资助项目National Natural Science Foundation of China[31670859] ; National Natural Science Foundation of China[81772243] ; National Natural Science Foundation of China[81803172] ; National Natural Science Foundation of China[81803167] ; National Natural Science Foundation of China[31800703] ; CAMS Innovation Fund for Medical Science[2017-I2M-1-016] ; CAMS Innovation Fund for Medical Science[2019-I2M-2-006] ; China Postdoctoral Science Foundation[2018M630106] ; Natural Science Foundation of Tianjin[18JCYBJC26800] ; Natural Science Foundation of Tianjin[18JCQNJC12300] ; Natural Science Foundation of Tianjin[17JCYBJC42700] ; Fundamental Research Funds for the Central Universities[10023201601602] ; Fundamental Research Funds for the Central Universities[3332019159] ; Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences[2017-1001-08] ; Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences[2018RC310020] ; CAMSInnovation Fund for Medical Science[2017-I2M-1-016] ; CAMSInnovation Fund for Medical Science[2019-I2M-2-006]
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000574332700026
出版者OXFORD UNIV PRESS
资助机构National Natural Science Foundation of China ; CAMS Innovation Fund for Medical Science ; China Postdoctoral Science Foundation ; Natural Science Foundation of Tianjin ; Fundamental Research Funds for the Central Universities ; Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences ; CAMSInnovation Fund for Medical Science
源URL[http://119.78.100.186/handle/113462/139693]  
专题中国科学院近代物理研究所
通讯作者Xu, Chang; Du, Liqing; Liu, Qiang
作者单位1.Chinese Acad Med Sci & Peking Union Med Coll, Inst Radiat Med, Tianjin Key Lab Radiat Med & Mol Nucl Med, Tianjin, Peoples R China
2.Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China
推荐引用方式
GB/T 7714		 Sun, Xiaohui,Wang, Yan,Ji, Kaihua,et al. NRF2 preserves genomic integrity by facilitating ATR activation and G2 cell cycle arrest[J]. NUCLEIC ACIDS RESEARCH,2020,48(16):9109-9123.
APA Sun, Xiaohui.,Wang, Yan.,Ji, Kaihua.,Liu, Yang.,Kong, Yangyang.,...&Liu, Qiang.(2020).NRF2 preserves genomic integrity by facilitating ATR activation and G2 cell cycle arrest.NUCLEIC ACIDS RESEARCH,48(16),9109-9123.
MLA Sun, Xiaohui,et al."NRF2 preserves genomic integrity by facilitating ATR activation and G2 cell cycle arrest".NUCLEIC ACIDS RESEARCH 48.16(2020):9109-9123.

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来源：近代物理研究所

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