title: Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry.
abstract: BACKGROUND
  Poly(ADP-ribose) polymerases (PARPs) catalyze the formation of poly(ADP-ribose) (pADPr), a post-translational modification involved in several important biological processes, namely surveillance of genome integrity, cell cycle progression, initiation of the DNA damage response, apoptosis, and regulation of transcription. Poly(ADP-ribose) glycohydrolase (PARG), on the other hand, catabolizes pADPr and thereby accounts for the transient nature of poly(ADP-ribosyl)ation. Our investigation of the interactomes of PARP-1, PARP-2, and PARG by affinity-purification mass spectrometry (AP-MS) aimed, on the one hand, to confirm current knowledge on these interactomes and, on the other hand, to discover new protein partners which could offer insights into PARPs and PARG functions.
  
  
  RESULTS
  PARP-1, PARP-2, and PARG were immunoprecipitated from human cells, and pulled-down proteins were separated by gel electrophoresis prior to in-gel trypsin digestion. Peptides were identified by tandem mass spectrometry. Our AP-MS experiments resulted in the identifications of 179 interactions, 139 of which are novel interactions. Gene Ontology analysis of the identified protein interactors points to five biological processes in which PARP-1, PARP-2 and PARG may be involved: RNA metabolism for PARP-1, PARP-2 and PARG; DNA repair and apoptosis for PARP-1 and PARP-2; and glycolysis and cell cycle for PARP-1.
  
  
  CONCLUSIONS
  This study reveals several novel protein partners for PARP-1, PARP-2 and PARG. It provides a global view of the interactomes of these proteins as well as a roadmap to establish the systems biology of poly(ADP-ribose) metabolism.
authors.affiliation: Axe cancer, CHUQ Research Center, Faculty of Medicine, Laval University, 2705 Boulevard Laurier, Québec, Canada, G1V 4G2. guy.poirier@crchul.ulaval.ca.
authors.forename: Maxim
authors.initials: M
authors.lastname: Isabelle
authors.forename: Xavier
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authors.lastname: Moreel
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Gagné
authors.forename: Michèle
authors.initials: M
authors.lastname: Rouleau
authors.forename: Chantal
authors.initials: C
authors.lastname: Ethier
authors.forename: Pierre
authors.initials: P
authors.lastname: Gagné
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hendzel
authors.forename: Guy G
authors.initials: GG
authors.lastname: Poirier
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