Jean Philippe Gagné

Proteomics approaches to study poly(ADP-ribosyl)ation

Abstract:
Poly(ADP-ribosyl)ation is a posttranslationnal modification created by the successive addition of ADP-ribose moieties onto an acceptor protein substrate to form a branched and heterogeneous polymer (pADPr). The biochemical characterization of all the members of the PARPs family is incomplete but an important observation may now be made: PARPs present a wide range of functional protein domains. Consistently, it is logical to believe that this surprising variety will be responsible for divergent functions in several cellular pathways. Poly(ADP-ribosyl)ation, although being a crucial modification involved in the regulation of genome integrity and cell survival, is not limited to nuclear functions anymore but appears more and more as an event which can take place in an extra-nuclear physiological context. Furthermore, noncovalent pADPr-binding, a phenomenon that can impact on protein’s functions, has started to reveal its important contribution to pADPr-dependent pathways. The major part of this work was aimed at the identification of PARG interaction partners to have insights on the pADPr-dependent pathways and functionally relevant protein:protein interactions that could be mediated by PARG-interacting proteins. In addition, proteins associated with pADPr where targeted by proteomics approaches, whether it is in a covalent or noncovalent way or part of pADPr-containing multiprotein complexes. Finally, proteomics studies were conducted to investigate the phosphorylation state of PARP-1 and PARG with consequences on biological functions

PhD in co-tutelle :
Université de Rennes1 (France) & Université Laval de Quebec (Canada)

Financial support:
Fonds de Recherche en Santé du Québec (FRSQ) & Instituts de recherche en Santé du Canada (IRSC) & Ministère des Relation Internationales du Québec & Ministère de la Recherche Française.

Committee : April 21st  2009
El Bachir Affar
Michel Lebel
Denis Beauchamp
Régis Giet
Guy Poirier (PhD co-director)
Claude Prigent (PhD co-director)

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