IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-11795-5.html
   My bibliography  Save this article

hCINAP regulates the DNA-damage response and mediates the resistance of acute myelocytic leukemia cells to therapy

Author

Listed:
  • Ruidan Xu

    (Peking University
    Peking University)

  • Shuyu Yu

    (Peking University
    Peking University)

  • Dan Zhu

    (Peking University
    Peking University)

  • Xinping Huang

    (Peking University
    Peking University)

  • Yuqi Xu

    (Peking University)

  • Yimin Lao

    (Shanghai Jiao Tong University School of Medicine)

  • Yonglu Tian

    (Peking University
    Peking University)

  • Jinfang Zhang

    (Peking University
    Peking University)

  • Zefang Tang

    (Peking University)

  • Zemin Zhang

    (Peking University)

  • Jing Yi

    (Shanghai Jiao Tong University School of Medicine)

  • Hong-Hu Zhu

    (Peking University)

  • Xiaofeng Zheng

    (Peking University
    Peking University)

Abstract

Acute myeloid leukemia (AML) is a genetically heterogeneous malignant disorder of the hematopoietic system, characterized by the accumulation of DNA-damaged immature myeloid precursors. Here, we find that hCINAP is involved in the repair of double-stranded DNA breaks (DSB) and that its expression correlates with AML prognosis. Following DSB, hCINAP is recruited to damage sites where it promotes SENP3-dependent deSUMOylation of NPM1. This in turn results in the dissociation of RAP80 from the damage site and CTIP-dependent DNA resection and homologous recombination. NPM1 SUMOylation is required for recruitment of DNA repair proteins at the early stage of DNA-damage response (DDR), and SUMOylated NPM1 impacts the assembly of the BRCA1 complex. Knockdown of hCINAP also sensitizes a patient-derived xenograft (PDX) mouse model to chemotherapy. In clinical AML samples, low hCINAP expression is associated with a higher overall survival rate in patients. These results provide mechanistic insight into the function of hCINAP during the DNA-damage response and its role in AML resistance to therapy.

Suggested Citation

  • Ruidan Xu & Shuyu Yu & Dan Zhu & Xinping Huang & Yuqi Xu & Yimin Lao & Yonglu Tian & Jinfang Zhang & Zefang Tang & Zemin Zhang & Jing Yi & Hong-Hu Zhu & Xiaofeng Zheng, 2019. "hCINAP regulates the DNA-damage response and mediates the resistance of acute myelocytic leukemia cells to therapy," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11795-5
    DOI: 10.1038/s41467-019-11795-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-11795-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-11795-5?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:10:y:2019:i:1:d:10.1038_s41467-019-11795-5. 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.