IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-25252-9.html
   My bibliography  Save this article

PARylation prevents the proteasomal degradation of topoisomerase I DNA-protein crosslinks and induces their deubiquitylation

Author

Listed:
  • Yilun Sun

    (National Cancer Institute, NIH)

  • Jiji Chen

    (National Institute of Biomedical Imaging and Bioengineering, NIH)

  • Shar-yin N. Huang

    (National Cancer Institute, NIH)

  • Yijun P. Su

    (National Institute of Biomedical Imaging and Bioengineering, NIH)

  • Wenjie Wang

    (National Cancer Institute, NIH)

  • Keli Agama

    (National Cancer Institute, NIH)

  • Sourav Saha

    (National Cancer Institute, NIH)

  • Lisa M. Jenkins

    (National Cancer Institute, NIH)

  • John M. Pascal

    (Université de Montréal)

  • Yves Pommier

    (National Cancer Institute, NIH)

Abstract

Poly(ADP)-ribosylation (PARylation) regulates chromatin structure and recruits DNA repair proteins. Using single-molecule fluorescence microscopy to track topoisomerase I (TOP1) in live cells, we found that sustained PARylation blocked the repair of TOP1 DNA-protein crosslinks (TOP1-DPCs) in a similar fashion as inhibition of the ubiquitin-proteasome system (UPS). PARylation of TOP1-DPC was readily revealed by inhibiting poly(ADP-ribose) glycohydrolase (PARG), indicating the otherwise transient and reversible PARylation of the DPCs. As the UPS is a key repair mechanism for TOP1-DPCs, we investigated the impact of TOP1-DPC PARylation on the proteasome and found that the proteasome is unable to associate with and digest PARylated TOP1-DPCs. In addition, PARylation recruits the deubiquitylating enzyme USP7 to reverse the ubiquitylation of PARylated TOP1-DPCs. Our work identifies PARG as repair factor for TOP1-DPCs by enabling the proteasomal digestion of TOP1-DPCs. It also suggests the potential regulatory role of PARylation for the repair of a broad range of DPCs.

Suggested Citation

  • Yilun Sun & Jiji Chen & Shar-yin N. Huang & Yijun P. Su & Wenjie Wang & Keli Agama & Sourav Saha & Lisa M. Jenkins & John M. Pascal & Yves Pommier, 2021. "PARylation prevents the proteasomal degradation of topoisomerase I DNA-protein crosslinks and induces their deubiquitylation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25252-9
    DOI: 10.1038/s41467-021-25252-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-25252-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-25252-9?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. Zita Fábián & Ellen S. Kakulidis & Ivo A. Hendriks & Ulrike Kühbacher & Nicolai B. Larsen & Marta Oliva-Santiago & Junhui Wang & Xueyuan Leng & A. Barbara Dirac-Svejstrup & Jesper Q. Svejstrup & Micha, 2024. "PARP1-dependent DNA-protein crosslink repair," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Yilun Sun & Simone A. Baechler & Xiaohu Zhang & Suresh Kumar & Valentina M. Factor & Yasuhiro Arakawa & Cindy H. Chau & Kanako Okamoto & Anup Parikh & Bob Walker & Yijun P. Su & Jiji Chen & Tabitha Ti, 2023. "Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Diana Rubio-Contreras & Fernando Gómez-Herreros, 2023. "TDP1 suppresses chromosomal translocations and cell death induced by abortive TOP1 activity during gene transcription," Nature Communications, Nature, vol. 14(1), pages 1-14, 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:12:y:2021:i:1:d:10.1038_s41467-021-25252-9. 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.