Serine is the major residue for ADP-ribosylation upon DNA damage

  1. Luca Palazzo
  2. Orsolya Leidecker
  3. Evgeniia Prokhorova
  4. Helen Dauben
  5. Ivan Matic  Is a corresponding author
  6. Ivan Ahel  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. Max Planck Institute for Biology of Ageing, Germany

Abstract

PARPs are a family of enzymes that synthesise ADP-ribosylation (ADPr), a reversible modification of proteins that regulates many different cellular processes. Several mammalian PARPs are known to regulate the DNA damage response, but it is not clear which amino acids in proteins are the primary ADPr targets. Previously we reported that ARH3 reverses the newly discovered type of ADPr (ADPr on serine residues; Ser-ADPr) and developed tools to analyse this modification (Fontana et al, 2017). Here we show that Ser-ADPr represents the major fraction of ADPr synthesised after DNA damage in mammalian cells and that globally Ser-ADPr is dependent on HPF1, PARP1 and ARH3. In the absence of HPF1, glutamate/aspartate become the main target residues for ADPr. Furthermore, we describe a method for site-specific validation of serine ADP-ribosylated substrates in cells. Our study establishes serine as the primary form of ADPr in DNA damage signalling.

Article and author information

Author details

  1. Luca Palazzo

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5556-5549
  2. Orsolya Leidecker

    Max Planck Institute for Biology of Ageing, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Evgeniia Prokhorova

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5467-5586
  4. Helen Dauben

    Max Planck Institute for Biology of Ageing, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Ivan Matic

    Max Planck Institute for Biology of Ageing, Cologne, Germany
    For correspondence
    imatic@age.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0170-7991
  6. Ivan Ahel

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    For correspondence
    ivan.ahel@path.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9446-3756

Funding

Wellcome (101794)

  • Ivan Ahel

Cancer Research UK (C35050/A22284)

  • Ivan Ahel

Horizon 2020 Framework Programme (657501)

  • Ivan Matic

Deutsche Forschungsgemeinschaft (EXC 229)

  • Ivan Matic

Horizon 2020 Framework Programme (281739)

  • Ivan Ahel

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ivan Dikic, Goethe University Frankfurt, Germany

Publication history

  1. Received: December 14, 2017
  2. Accepted: February 23, 2018
  3. Accepted Manuscript published: February 26, 2018 (version 1)
  4. Version of Record published: March 5, 2018 (version 2)

Copyright

© 2018, Palazzo et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Luca Palazzo
  2. Orsolya Leidecker
  3. Evgeniia Prokhorova
  4. Helen Dauben
  5. Ivan Matic
  6. Ivan Ahel
(2018)
Serine is the major residue for ADP-ribosylation upon DNA damage
eLife 7:e34334.
https://doi.org/10.7554/eLife.34334
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