IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15858-w.html
   My bibliography  Save this article

Real-time monitoring of PARP1-dependent PARylation by ATR-FTIR spectroscopy

Author

Listed:
  • Annika Krüger

    (University of Konstanz
    University of Konstanz)

  • Alexander Bürkle

    (University of Konstanz)

  • Karin Hauser

    (University of Konstanz)

  • Aswin Mangerich

    (University of Konstanz)

Abstract

Poly-ADP-ribosylation (PARylation) is a fully reversible post-translational modification with key roles in cellular physiology. Due to the multi-domain structure of poly(ADP-ribose) polymerase-1 (PARP1) and the highly dynamic nature of the PARylation reaction, studies on the biochemical mechanism and structural dynamics remain challenging. Here, we report label-free, time-resolved monitoring of PARP1-dependent PARylation using ATR-FTIR spectroscopy. This includes PARP1 activation by binding to DNA strand break models, NAD+ substrate binding, PAR formation, and dissociation of automodified PARP1 from DNA. Analyses of PARP1 activation at different DNA models demonstrate a strong positive correlation of PARylation and PARP1 dissociation, with the strongest effects observed for DNA nicks and 3’ phosphorylated ends. Moreover, by examining dynamic structural changes of PARP1, we reveal changes in the secondary structure of PARP1 induced by NAD+ and PARP inhibitor binding. In summary, this approach enables holistic and dynamic insights into PARP1-dependent PARylation with molecular and temporal resolution.

Suggested Citation

  • Annika Krüger & Alexander Bürkle & Karin Hauser & Aswin Mangerich, 2020. "Real-time monitoring of PARP1-dependent PARylation by ATR-FTIR spectroscopy," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15858-w
    DOI: 10.1038/s41467-020-15858-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15858-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-15858-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
    ---><---

    Citations

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


    Cited by:

    1. Haibo Yang & Emily M. Lachtara & Xiaojuan Ran & Jessica Hopkins & Parasvi S. Patel & Xueping Zhu & Yao Xiao & Laiyee Phoon & Boya Gao & Lee Zou & Michael S. Lawrence & Li Lan, 2023. "The RNA m5C modification in R-loops as an off switch of Alt-NHEJ," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Simon D. Schwarz & Jianming Xu & Kapila Gunasekera & David Schürmann & Cathrine B. Vågbø & Elena Ferrari & Geir Slupphaug & Michael O. Hottiger & Primo Schär & Roland Steinacher, 2024. "Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation," Nature Communications, Nature, vol. 15(1), pages 1-13, 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:11:y:2020:i:1:d:10.1038_s41467-020-15858-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.

    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.