Serine is the major residue for ADP-ribosylation upon DNA damage
- University of Oxford, United Kingdom
- 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
Evgeniia Prokhorova
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.
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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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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