PARP2 mediates branched poly ADP-ribosylation in response to DNA damage.
Fiche publication
Date publication
août 2018
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DANTZER Françoise
Tous les auteurs :
Chen Q, Kassab MA, Dantzer F, Yu X
Lien Pubmed
Résumé
Poly(ADP-ribosyl)ation (PARylation) is a posttranslational modification involved in multiple biological processes, including DNA damage repair. This modification is catalyzed by poly(ADP-ribose) polymerase (PARP) family of enzymes. PARylation is composed of both linear and branched polymers of poly(ADP-ribose) (PAR). However, the biochemical mechanism of polymerization and biological functions of branched PAR chains are elusive. Here we show that PARP2 is preferentially activated by PAR and subsequently catalyzes branched PAR chain synthesis. Notably, the direct binding to PAR by the N-terminus of PARP2 promotes the enzymatic activity of PARP2 toward the branched PAR chain synthesis. Moreover, the PBZ domain of APLF recognizes the branched PAR chain and regulates chromatin remodeling to DNA damage response. This unique feature of PAR-dependent PARP2 activation and subsequent PARylation mediates the participation of PARP2 in DNA damage repair. Thus, our results reveal an important molecular mechanism of branched PAR synthesis and a key biological function of branched PARylation.
Mots clés
Animals, Cell Line, Tumor, DNA Damage, DNA-(Apurinic or Apyrimidinic Site) Lyase, chemistry, Fibroblasts, metabolism, Histones, metabolism, Humans, Mice, Poly (ADP-Ribose) Polymerase-1, metabolism, Poly ADP Ribosylation, Poly(ADP-ribose) Polymerases, chemistry, Poly-ADP-Ribose Binding Proteins, chemistry, Polymerization
Référence
Nat Commun. 2018 Aug 13;9(1):3233