Serine ADP-ribosylation reversal by the hydrolase ARH3

Elife. 2017 Jun 26;6:e28533. doi: 10.7554/eLife.28533.

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.

Keywords: ADP-ribose; ADP-ribosylation; ARH3; PARP; biochemistry; human; macrodomain.

MeSH terms

  • ADP-Ribosylation*
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Glycoside Hydrolases / metabolism*
  • Histones / metabolism
  • Humans
  • Nuclear Proteins / metabolism*
  • Poly (ADP-Ribose) Polymerase-1 / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Processing, Post-Translational*
  • Proteome / analysis
  • Proteomics
  • Serine / metabolism*

Substances

  • Carrier Proteins
  • HPF1 protein, human
  • Histones
  • Nuclear Proteins
  • Proteome
  • Serine
  • PARP1 protein, human
  • PARP2 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Glycoside Hydrolases
  • ADPRS protein, human