GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability.
Wang Lai HuLei JinAn XuYu Fang WangRick F ThorneYuan Yuan ZhangMian WuPublished in: Nature cell biology (2018)
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.
Keyphrases
- long non coding rna
- poor prognosis
- dna damage response
- copy number
- breast cancer risk
- binding protein
- stress induced
- dna damage
- cancer therapy
- oxidative stress
- dna repair
- papillary thyroid
- cell death
- endothelial cells
- circulating tumor
- cell free
- squamous cell carcinoma
- cell cycle arrest
- gene expression
- childhood cancer
- single molecule
- network analysis
- heat stress
- dna methylation
- circulating tumor cells
- transcription factor
- dna binding
- genome wide analysis
- young adults
- nucleic acid
- tissue engineering