%0 Journal Article
%T Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry
%A Maxim Isabelle
%A Xavier Moreel
%A Jean-Philippe Gagn¨¦
%A Mich¨¨le Rouleau
%A Chantal Ethier
%A Pierre Gagn¨¦
%A Michael J Hendzel
%A Guy G Poirier
%J Proteome Science
%D 2010
%I BioMed Central
%R 10.1186/1477-5956-8-22
%X 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.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.Poly(ADP-ribose) polymerases (PARPs) catalyze the formation of poly(ADP-ribose) (pADPr), a protein 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 (reviewed in [1]). Recently Kleine et al. [2] limited the PARP family to PARPs possessing the HYE catalytic core motif as well as a long ¦Â4/¦Â5 loop, namely PARP-1, -2, -3, tankyrase-1 and -2, and vault-PARP. All other putative PARP family members were re-classified as mono-ADP-ribosyltransferases (PARP-6, -7, -8, -10, -11, -12, -14, -15, and -16) or catalytically inactive members (PARP-9 and -13). Poly(ADP-ribose) glycohydrolase (PARG), on the other hand, catabolizes pADPr and thereby accounts for the transient nature of poly(ADP-ribosyl)ation.In this study, we chose to investigate PARP-1 and PARP-2 because of their pivotal role in the maintenance of genome integrity, and PARG to cover both the synthesis and degradation components of pADPr metabolism. Through their strand break-dependent PARP activity, both PARP-1 and P
%U http://www.proteomesci.com/content/8/1/22