IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-25827-6.html
   My bibliography  Save this article

A novel lncRNA Discn fine-tunes replication protein A (RPA) availability to promote genomic stability

Author

Listed:
  • Lin Wang

    (Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming Institute of Zoology, Chinese Academy of Sciences)

  • Jingzheng Li

    (Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Hu Zhou

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Weidao Zhang

    (Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming Institute of Zoology, Chinese Academy of Sciences)

  • Jing Gao

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Ping Zheng

    (Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming Institute of Zoology, Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

RPA is a master regulator of DNA metabolism and RPA availability acts as a rate-limiting factor. While numerous studies focused on the post-translational regulations of RPA for its functions, little is known regarding how RPA availability is controlled. Here we identify a novel lncRNA Discn as the guardian of RPA availability in stem cells. Discn is induced upon genotoxic stress and binds to neucleolin (NCL) in the nucleolus. This prevents NCL from translocation into nucleoplasm and avoids undesirable NCL-mediated RPA sequestration. Thus, Discn-NCL-RPA pathway preserves a sufficient RPA pool for DNA replication stress response and repair. Discn loss causes massive genome instability in mouse embryonic stem cells and neural stem/progenigor cells. Mice depleted of Discn display newborn death and brain dysfunctions due to DNA damage accumulation and associated inflammatory reactions. Our findings uncover a key regulator of DNA metabolism and provide new clue to understand the chemoresistance in cancer treatment.

Suggested Citation

  • Lin Wang & Jingzheng Li & Hu Zhou & Weidao Zhang & Jing Gao & Ping Zheng, 2021. "A novel lncRNA Discn fine-tunes replication protein A (RPA) availability to promote genomic stability," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25827-6
    DOI: 10.1038/s41467-021-25827-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-25827-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-25827-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25827-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.