The list of longnoncodingrnas(lncrnas) involved in the p53pathway of the DNA damage response is rapidly expanding, but whether lncrnas play a role in maintaining the de novo structure of DNA is unknown. Here we dem...
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The list of longnoncodingrnas(lncrnas) involved in the p53pathway of the DNA damage response is rapidly expanding, but whether lncrnas play a role in maintaining the de novo structure of DNA is unknown. Here we demonstrate that the p53-responsive lncrnaguardin 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-23 a. Moreover, guardin also sustains breast cancer 1(BRCA1) stability by acting as an rna scaffold to facilitate the heterodimerisation 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. guardin may therefore constitute a target for cancer treatment.
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