Serine ADP-ribosylation reversal by the hydrolase ARH3

Abstract

ADP-ribosylation (ADPr) is a posttranslational modification (PTM) of proteins that controls many cellular processes, including DNA repair, transcription, chromatin regulation and mitosis. A number of proteins catalyse the transfer and hydrolysis of ADPr, and also specify how and when the modification is conjugated to the targets. We recently discovered a new form of ADPr that is attached to serine residues in target proteins (Ser-ADPr) and showed that this PTM is specifically made by PARP1/HPF1 and PARP2/HPF1 complexes. In this work, we found by quantitative proteomics that histone Ser-ADPr is reversible in cells during response to DNA damage. By screening for the hydrolase that is responsible for the reversal of Ser-ADPr, we identified ARH3/ADPRHL2 as capable of efficiently and specifically removing Ser-ADPr of histones and other proteins. We further showed that Ser-ADPr is a major PTM in cells after DNA damage and that this signalling is dependent on ARH3.

Article and author information

Author details

Pietro Fontana

Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Juan José Bonfiglio

Max Planck Institute for Biology of Ageing, Cologne, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7767-0799
Luca Palazzo

Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5556-5549
Edward Bartlett

Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom

Competing interests
The authors declare that no competing interests exist.
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.
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.

"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

Deutsche Forschungsgemeinschaft (EXC 229)

Ivan Matic

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

Reviewing Editor

Ivan Dikic, Goethe University Frankfurt, Germany

Publication history

Received: May 11, 2017
Accepted: June 23, 2017
Accepted Manuscript published: June 26, 2017 (version 1)
Accepted Manuscript updated: June 29, 2017 (version 2)
Version of Record published: August 10, 2017 (version 3)

Copyright

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.