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Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose

Author

Listed:
  • Max S. Kloet

    (Leiden University Medical Centre)

  • Chatrin Chatrin

    (University of Oxford)

  • Rishov Mukhopadhyay

    (Leiden University Medical Centre)

  • Bianca D. M. van Tol

    (Leiden University Medical Centre)

  • Rebecca Smith

    (University of Oxford)

  • Sarah A. Rotman

    (Leiden University Medical Centre)

  • Rayman T. N. Tjokrodirijo

    (Leiden University Medical Centre)

  • Kang Zhu

    (University of Oxford)

  • Andrii Gorelik

    (University of Oxford)

  • Lucy Maginn

    (University of Oxford)

  • Paul R. Elliott

    (University of Oxford)

  • Peter A. van Veelen

    (Leiden University Medical Centre)

  • Dragana Ahel

    (University of Oxford)

  • Ivan Ahel

    (University of Oxford)

  • Gerbrand J. van der Heden van Noort

    (Leiden University Medical Centre)

Abstract

Crosstalk between the post-translational modification processes of ubiquitination and ADP-ribosylation occurs in DNA-damage- and immune-responses, in addition the physical linkage of ADP-ribose and ubiquitin is found during bacterial infection. Here, we study the ubiquitination of ADP-ribose mediated by human Deltex E3 ligases and the subsequent fate of the formed hybrid post-translational modification. We prepare a non-hydrolysable ADPr-Ub probe that we employ in a proteomics approach and identify RNF114 as an interacting protein. Using biophysical and biochemical experiments, we validate that RNF114 preferentially interacts with ubiquitinated ADP-ribose over non-modified ubiquitin. Subsequently, RNF114 can elongate the ubiquitinated ADP-ribose with a K11-linked ubiquitin chain. Using domain deletion analysis, we pinpoint the tandem zinc fingers and ubiquitin interacting motif (ZnF2 + ZnF3+UIM) domains of RNF114 to be crucial for recognising ubiquitinated ADP-ribose. Moreover, these domains are essential for the recruitment of RNF114 to the sites of laser-induced DNA damage.

Suggested Citation

  • Max S. Kloet & Chatrin Chatrin & Rishov Mukhopadhyay & Bianca D. M. van Tol & Rebecca Smith & Sarah A. Rotman & Rayman T. N. Tjokrodirijo & Kang Zhu & Andrii Gorelik & Lucy Maginn & Paul R. Elliott & , 2025. "Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61111-7
    DOI: 10.1038/s41467-025-61111-7
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