IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9088.html

Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)

Author

Listed:
  • Matthias Altmeyer

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich)

  • Kai J. Neelsen

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Federico Teloni

    (Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich)

  • Irina Pozdnyakova

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Stefania Pellegrino

    (Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich)

  • Merete Grøfte

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Maj-Britt Druedahl Rask

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Werner Streicher

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen
    Present address: Novozymes A/S, Krogshoejvej 36, DK-2880 Bagsverd, Denmark)

  • Stephanie Jungmichel

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Michael Lund Nielsen

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Jiri Lukas

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen)

Abstract

Intrinsically disordered proteins can phase separate from the soluble intracellular space, and tend to aggregate under pathological conditions. The physiological functions and molecular triggers of liquid demixing by phase separation are not well understood. Here we show in vitro and in vivo that the nucleic acid-mimicking biopolymer poly(ADP-ribose) (PAR) nucleates intracellular liquid demixing. PAR levels are markedly induced at sites of DNA damage, and we provide evidence that PAR-seeded liquid demixing results in rapid, yet transient and fully reversible assembly of various intrinsically disordered proteins at DNA break sites. Demixing, which relies on electrostatic interactions between positively charged RGG repeats and negatively charged PAR, is amplified by aggregation-prone prion-like domains, and orchestrates the earliest cellular responses to DNA breakage. We propose that PAR-seeded liquid demixing is a general mechanism to dynamically reorganize the soluble nuclear space with implications for pathological protein aggregation caused by derailed phase separation.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9088
    DOI: 10.1038/ncomms9088
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9088
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9088?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. 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.
    2. Zhaowei Yu & Qi Wang & Qichen Zhang & Yawen Tian & Guo Yan & Jidong Zhu & Guangya Zhu & Yong Zhang, 2024. "Decoding the genomic landscape of chromatin-associated biomolecular condensates," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. 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.
    4. Yingda Ge & Tapas Paul & Margarita Gordiychuk & Nilimesh Das & Yaojun Zhang & Sua Myong, 2025. "FUS nanoclusters are a distinct state within the dilute phase," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    5. Umeshkumar Vekariya & Leonid Minakhin & Gurushankar Chandramouly & Mrityunjay Tyagi & Tatiana Kent & Katherine Sullivan-Reed & Jessica Atkins & Douglas Ralph & Margaret Nieborowska-Skorska & Anna-Mari, 2024. "PARG is essential for Polθ-mediated DNA end-joining by removing repressive poly-ADP-ribose marks," Nature Communications, Nature, vol. 15(1), pages 1-18, 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:6:y:2015:i:1:d:10.1038_ncomms9088. 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.