GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability

被引：239

作者：

Hu, Wang Lai ^{[1
,2
,3
]}

Jin, Lei ^{[4
]}

Xu, An ^{[1
]}

Wang, Yu Fang ^{[5
]}

Thorne, Rick F. ^{[2
,6
]}

Zhang, Xu Dong ^{[2
,4
]}

Wu, Mian ^{[1
,2
]}

机构：

[1] Univ Sci & Technol China, CAS Ctr Excellence Cell & Mol Biol, Innovat Ctr Cell Signalling Network,Sch Life Sci, Chinese Acad Sci CAS,Key Lab Innate Immun & Chron, Hefei, Peoples R China

[2] Henan Prov Peoples Hosp, Translat Res Inst, Zhengzhou, Henan, Peoples R China

[3] Anhui Med Univ, Dept Immunol, Hefei, Anhui, Peoples R China

[4] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW, Australia

[5] Sichuan Univ, Sch Preclin & Forens Med, Dept Pathophysiol, Chengdu, Sichuan, Peoples R China

[6] Univ Newcastle, Sch Environm & Life Sci, Newcastle, NSW, Australia

来源：

NATURE CELL BIOLOGY | 2018年 / 20卷 / 04期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

ONCOGENE-INDUCED SENESCENCE; DNA-DAMAGE; HOMOLOGOUS RECOMBINATION; BREAST-CANCER; CELLULAR SENESCENCE; TUMOR SUPPRESSION; REPAIR PATHWAY; HUMAN-MELANOMA; P53; FAMILY; IN-VIVO;

D O I：

10.1038/s41556-018-0066-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：492 / +

页数：13

共 69 条

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