Poly(ADP-ribose)polymerases (PARPs) are found mostly in eukaryotes and catalyze the transfer of multiple ADP-ribose molecules to target proteins. As with mono(ADP-ribosyl)ation, the source of ADP-ribose is NAD+. PARPs use a catalytic triad of His-Tyr-Glu to facilitate binding of NAD+ and positioning of the end of the existing poly(ADP-ribose) chain on the target protein; the Glu facilitates catalysis and formation of a (1''¡ú2') O-glycosidic linkage between two ribose molecules. There are several other enzymes that recognize poly(ADP-ribose) chains, hydrolyse them or form branches; over 800 proteins have been annotated to contain the loosely defined poly(ADP-ribose) binding motif; therefore, in addition to this modification altering target protein conformation and structure, it may also be used as a tag to recruit other proteins or for regulation of the target protein.

Reference
Wiki: Poly(ADP-ribosyl)ation

    Mono(ADP-ribosyl)transferases commonly catalyze the addition of ADP-ribose to arginine side chains using a highly conserved R-S-EXE motif of the enzyme. The reaction proceeds by breaking the bond between nicotinamide and ribose to form an oxonium ion. Next, the arginine side chain of the target protein then acts a nucleophile, attacking the electrophilic carbon adjacent to the oxonium ion. In order for this step to occur, the arginine nucleophile is deprotonated by a glutamate residue on the catalyzing enzyme[disputed ¨C discuss]. Another conserved glutamate residue forms a hydrogen bond with one of the hydroxyl groups on the ribose chain to further facilitate this nucleophilic attack. As a result of the cleavage reaction, nicotinamide is released. The modification can be reversed by (ADP-ribosyl)hydrolases, which cleave the N-glycosidic bond between arginine and ribose to release ADP-ribose and unmodified protein; NAD+ is not restored by the reverse reaction.

Reference
Wiki: Mono(ADP-ribosyl)ation

    PARylation is a transient posttranslational modification and is quickly degraded by dePARylation enzymes, such as poly(ADP-ribose) glycohydrolase (PARG) . PARG specifically hydrolyzes the glycosidic bonds between ADP-ribose units in PAR chains and is the major dePARylation enzyme that accounts for ~90% of dePARylation activity . Notably, similar to PARPs, PARG also facilitates both DNA double-strand break (DSB) and single-strand break (SSB) repair . Following DNA damage, a number of DNA damage response factors recognize PARylation and are recruited by PARylation to the proximity of DNA lesions . However, PARylation has to be digested so that DNA damage machinery directly recognizes DNA lesions and repairs lesions . Otherwise, the repair machineries will be trapped by PARylation at the vicinity of DNA lesions. Thus, dePARylation is an immediate downstream step of PARylation in DNA repair, and suppression of dePARylation will affect PARylation-dependent DNA repair. It indicates that targeting dePARylation, similar to targeting PARPs, may selectively kill tumor cells with DNA repair defects.

Reference
Pubmed: Chen SH, Yu X. Targeting dePARylation selectively suppresses DNA repair-defective and PARP inhibitor-resistant malignancies. Sci Adv. 2019 Apr 10;5(4):eaav4340. doi: 10.1126/sciadv.aav4340.

    ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis. Improper ADP-ribosylation has been implicated in some forms of cancer. It is also the basis for the toxicity of bacterial compounds such as cholera toxin, diphtheria toxin, and others.

Reference
Wiki: ADP-ribosylation