Article Dans Une Revue Nature Communications Année : 2018

PARP2 mediates branched poly ADP-ribosylation in response to DNA damage

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.
Fichier principal
Vignette du fichier
2018_NatCommun_Chem.Q.pdf (1) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
licence

Dates et versions

hal-02369065 , version 1 (21-02-2025)

Licence

Identifiants

Citer

Qian Chen, Muzaffer Ahmad Kassab, Françoise Dantzer, Xiaochun Yu. PARP2 mediates branched poly ADP-ribosylation in response to DNA damage. Nature Communications, 2018, 9 (1), pp.1615-1630. ⟨10.1038/s41467-018-05588-5⟩. ⟨hal-02369065⟩
26 Consultations
0 Téléchargements

Altmetric

Partager

More