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


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Article Info

DATE

2018-03-28

AUTHORS

Wang Lai Hu, Lei Jin, An Xu, Yu Fang Wang, Rick F. Thorne, Xu Dong Zhang, Mian Wu

ABSTRACT

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. More... »

PAGES

492-502

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  • Journal

    TITLE

    Nature Cell Biology

    ISSUE

    4

    VOLUME

    20

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41556-018-0066-7

    DOI

    http://dx.doi.org/10.1038/s41556-018-0066-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1101824165

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29593331


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