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
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
Version 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
© 2017, Ahel 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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Further reading
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- Biochemistry and Chemical Biology
The modification of serines by molecules of ADP-ribose plays an important role in signaling that the DNA in a cell has been damaged and needs to be repaired.
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- Biochemistry and Chemical Biology
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