IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30303-w.html
   My bibliography  Save this article

MRNIP condensates promote DNA double-strand break sensing and end resection

Author

Listed:
  • Yun-Long Wang

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University
    the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Wan-Wen Zhao

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Shao-Mei Bai

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Li-Li Feng

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Shu-Ying Bie

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Li Gong

    (Sun Yat-sen University)

  • Fang Wang

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Ming-Biao Wei

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Wei-Xing Feng

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Xiao-Lin Pang

    (the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Cao-Litao Qin

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Xin-Ke Yin

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University)

  • Ying-Nai Wang

    (The University of Texas MD Anderson Cancer Center)

  • Weihua Zhou

    (University of Michigan)

  • Daniel R. Wahl

    (University of Michigan
    University of Michigan)

  • Quentin Liu

    (Dalian Medical University
    Sun Yat-sen University)

  • Ming Chen

    (Sun Yat-sen University)

  • Mien-Chie Hung

    (The University of Texas MD Anderson Cancer Center
    China Medical University
    Asia University)

  • Xiang-Bo Wan

    (Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University
    the Sixth Affiliated Hospital, Sun Yat-sen University)

Abstract

The rapid recognition of DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex is critical for the initiation of DNA damage response and DSB end resection. Here, we show that MRN complex interacting protein (MRNIP) forms liquid-like condensates to promote homologous recombination-mediated DSB repair. The intrinsically disordered region is essential for MRNIP condensate formation. Mechanically, the MRN complex is compartmentalized and concentrated into MRNIP condensates in the nucleus. After DSB formation, MRNIP condensates move to the damaged DNA rapidly to accelerate the binding of DSB by the concentrated MRN complex, therefore inducing the autophosphorylation of ATM and subsequent activation of DNA damage response signaling. Meanwhile, MRNIP condensates-enhanced MRN complex loading further promotes DSB end resection. In addition, data from xenograft models and clinical samples confirm a correlation between MRNIP and radioresistance. Together, these results reveal an important role of MRNIP phase separation in DSB response and the MRN complex-mediated DSB end resection.

Suggested Citation

  • Yun-Long Wang & Wan-Wen Zhao & Shao-Mei Bai & Li-Li Feng & Shu-Ying Bie & Li Gong & Fang Wang & Ming-Biao Wei & Wei-Xing Feng & Xiao-Lin Pang & Cao-Litao Qin & Xin-Ke Yin & Ying-Nai Wang & Weihua Zhou, 2022. "MRNIP condensates promote DNA double-strand break sensing and end resection," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30303-w
    DOI: 10.1038/s41467-022-30303-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30303-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30303-w?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
    ---><---

    References listed on IDEAS

    as
    1. Roxanne Oshidari & Richard Huang & Maryam Medghalchi & Elizabeth Y. W. Tse & Nasser Ashgriz & Hyun O. Lee & Haley Wyatt & Karim Mekhail, 2020. "DNA repair by Rad52 liquid droplets," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    2. Matthias Altmeyer & Kai J. Neelsen & Federico Teloni & Irina Pozdnyakova & Stefania Pellegrino & Merete Grøfte & Maj-Britt Druedahl Rask & Werner Streicher & Stephanie Jungmichel & Michael Lund Nielse, 2015. "Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    3. Vivek Tripathi & Himanshi Agarwal & Swati Priya & Harish Batra & Priyanka Modi & Monica Pandey & Dhurjhoti Saha & Sathees C. Raghavan & Sagar Sengupta, 2018. "MRN complex-dependent recruitment of ubiquitylated BLM helicase to DSBs negatively regulates DNA repair pathways," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Judith Oehler & Carl A. Morrow & Matthew C. Whitby, 2023. "Gene duplication and deletion caused by over-replication at a fork barrier," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Marie-France Langelier & Ramya Billur & Aleksandr Sverzhinsky & Ben E. Black & John M. Pascal, 2021. "HPF1 dynamically controls the PARP1/2 balance between initiating and elongating ADP-ribose modifications," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Vera M. Kissling & Giordano Reginato & Eliana Bianco & Kristina Kasaciunaite & Janny Tilma & Gea Cereghetti & Natalie Schindler & Sung Sik Lee & Raphaël Guérois & Brian Luke & Ralf Seidel & Petr Cejka, 2022. "Mre11-Rad50 oligomerization promotes DNA double-strand break repair," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Jaigeeth Deveryshetty & Rahul Chadda & Jenna R. Mattice & Simrithaa Karunakaran & Michael J. Rau & Katherine Basore & Nilisha Pokhrel & Noah Englander & James A. J. Fitzpatrick & Brian Bothner & Edwin, 2023. "Yeast Rad52 is a homodecamer and possesses BRCA2-like bipartite Rad51 binding modes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    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:13:y:2022:i:1:d:10.1038_s41467-022-30303-w. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.