机构：[1]Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Centre for Excellence in Cell and Molecular Biology,Innovation Centre for Cell Signalling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China[2]Translational ResearchInstitute, Henan Provincial People’s Hospital, Zhengzhou, China[3]Department of Immunology, Anhui Medical University, Hefei, China[4]School of Medicineand Public Health, University of Newcastle, Callaghan, New South Wales, Australia[5]Department of Pathophysiology, School of Preclinical and ForensicMedicine, Sichuan University, Chengdu, China[6]School of Environmental and Life Sciences, University of Newcastle, Newcastle, New South Wales
The list of long non-coding RNAs (lncRNAs) involved in the p53 pathway of the DNA damage response is rapidly expanding, but whether lncRNAs have a role in maintaining the de novo structure of DNA is unknown. Here, we demonstrate that the p53-responsive lncRNA GUARDIN is important for maintaining genomic integrity under steady-state conditions and after exposure to exogenous genotoxic stress. GUARDIN is necessary for preventing chromosome end-to-end fusion through maintaining the expression of telomeric repeat-binding factor 2 (TRF2) by sequestering microRNA-23a. Moreover, GUARDIN also sustains breast cancer 1 (BRCA1) stability by acting as an RNA scaffold to facilitate the heterodimerization of BRCA1 and BRCA1-associated RING domain protein 1 (BARD1). As such, GUARDIN silencing triggered apoptosis and senescence, enhanced cytotoxicity of additional genotoxic stress and inhibited cancer xenograft growth. Thus, GUARDIN may constitute a target for cancer treatment.
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外文
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中科院(CAS)分区：
出版当年[2018]版：
大类|1 区生物
小类|1 区细胞生物学
最新[2023]版：
大类|1 区生物学
小类|1 区细胞生物学
第一作者：
第一作者机构：[1]Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Centre for Excellence in Cell and Molecular Biology,Innovation Centre for Cell Signalling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China[2]Translational ResearchInstitute, Henan Provincial People’s Hospital, Zhengzhou, China[3]Department of Immunology, Anhui Medical University, Hefei, China
共同第一作者：
通讯作者：
通讯机构：[1]Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Centre for Excellence in Cell and Molecular Biology,Innovation Centre for Cell Signalling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China[2]Translational ResearchInstitute, Henan Provincial People’s Hospital, Zhengzhou, China[4]School of Medicineand Public Health, University of Newcastle, Callaghan, New South Wales, Australia
推荐引用方式(GB/T 7714)：
Hu Wang Lai,Jin Lei,Xu An,et al.GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability.[J].Nature cell biology.2018,20(4):492-502.doi:10.1038/s41556-018-0066-7.
APA：
Hu Wang Lai,Jin Lei,Xu An,Wang Yu Fang,Thorne Rick F...&Wu Mian.(2018).GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability..Nature cell biology,20,(4)
MLA：
Hu Wang Lai,et al."GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability.".Nature cell biology 20..4(2018):492-502
生物