PARP3

PARP3 Background

The ADP ribosyl transferase [poly(ADP-ribose) polymerase] ARTD3(PARP3) ^[1] is a newly characterized member of the ARTD(PARP) family that catalyzes the reaction of ADP ribosylation, a key posttranslational modification of proteins involved in different signaling pathways from DNA damage to energy metabolism and organismal memory ^[2]. PARP3 shares high structural similarities with the DNA repair enzymes PARP1 and PARP2 and accordingly has been found to catalyze poly(ADP ribose) synthesis. Christian Boehler et al. identify PARP3 as a critical player in the stabilization of the mitotic spindle and in telomere integrity notably by associating and regulating the mitotic components NuMA and tankyrase 1 ^[2]. Both functions open stimulating prospects for specifically targeting PARP3 in cancer therapy. DNA-dependent PARP3 can modify DNA and form a specific primed structure for further use by the repair proteins. E. A. Belousova et al. demonstrated that gapped DNA that was ADP-ribosylated by PARP3 could be ligated to double-stranded DNA by DNA ligases ^[3]. Moreover, this ADP-ribosylated DNA could serve as a primed DNA substrate for PAR chain elongation by the purified proteins PARP1 and PARP2 as well as by cell-free extracts. We suggest that this ADP-ribose modification can be involved in cellular pathways that are important for cell survival in the process of double-strand break formation.

[1] Johansson M (Aug 1999). A human poly(ADP-ribose) polymerase gene family (ADPRTL): cDNA cloning of two novel poly(ADP-ribose) polymerase homologues [J]. Genomics. 57 (3): 442–5.
[2] Christian Boehler, Laurent R. Gauthier, et al. Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression [J]. PNAS February 15, 2011 108 (7) 2783-2788.
[3] E. A. Belousova, А. A. Ishchenko, et al. Dna is a New Target of Parp3 [J]. Scientific Reports volume 8, Article number: 4176 (2018).