PARP2

PARP2 Background

Poly [ADP-ribose] polymerase 2 is a protein in humans that is encoded by PARP2 gene ^[1][2]. PARP2 contains a catalytic domain homologous to that of poly (ADP-ribosyl) transferase and is capable of catalyzing a poly(ADP-ribosyl)ation reaction. Howevr, it lacks an N-terminal DNA binding domain that activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. The basic residues within the N-terminal region of this protein may bear potential DNA-binding properties, and may be involved in the nuclear and/or nucleolar targeting of the protein. There are two alternatively spliced transcript variants encoding distinct isoforms. PARP2 mediates the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. Qian Chen et al. showed that PARP2 is preferentially activated by PAR and subsequently catalyzes branched PAR chain synthesis ^[3]. 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, Their results reveal an important molecular mechanism of branched PAR synthesis and a key biological function of branched PARylation.

[1] Johansson M. A human poly(ADP-ribose) polymerase gene family (ADPRTL): cDNA cloning of two novel poly(ADP-ribose) polymerase homologues [J]. Genomics. 1999, 57 (3): 442–5.
[2] Yélamos J, Schreiber V, et al Toward specific functions of poly(ADP-ribose) polymerase-2 [J]. Trends in Molecular Medicine. 2008, 14 (4): 169–78.
[3] Qian Chen, Muzaffer Ahmad Kassab, et al. PARP2 mediates branched poly ADP-ribosylation in response to DNA damage [J]. Nature Communications volume 9, 2018, Article number: 3233.