- Title
- GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability
- Creator
- Hu, Wang Lai; Jin, Lei; Xu, An; Wang, Yu Fang; Thorne, Rick F.; Zhang, Xu Dong; Wu, Mian
- Relation
- Nature Cell Biology Vol. 20, Issue 4, p. 492-502
- Publisher Link
- http://dx.doi.org/10.1038/s41556-018-0066-7
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2018
- Description
- 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.
- Subject
- cancer; DNA damage response; non-coding RNAs; GUARDIN; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1466940
- Identifier
- uon:47696
- Identifier
- ISSN:1465-7392
- Language
- eng
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