A Double-Edged Sword: The Two Faces of PARylation

Abstract

Poly ADP-ribosylation (PARylation) is a post-translational modification process. Following the discovery of PARP-1, numerous studies have demonstrated the role of PARylation in the DNA damage and repair responses for cellular stress and DNA damage. Originally, studies on PARylation were confined to PARP-1 activation in the DNA repair pathway. However, the interplay between PARylation and DNA repair suggests that PARylation is important for the efficiency and accuracy of DNA repair. PARylation has contradicting roles; however, recent evidence implicates its importance in inflammation, metabolism, and cell death. These differences might be dependent on specific cellular conditions or experimental models used, and suggest that PARylation may play two opposing roles in cellular homeostasis. Understanding the role of PARylation in cellular function is not only important for identifying novel therapeutic approaches; it is also essential for gaining insight into the mechanisms of unexplored diseases. In this review, we discuss recent reports on the role of PARylation in mediating diverse cellular functions and homeostasis, such as DNA repair, inflammation, metabolism, and cell death.

Pathogenesis and clinical features of severe hepatitis E virus infection

“…There are two known forms of ADP-ribosylation: Poly (ADP-ribosyl) ation and mono (ADP-ribosyl) ation, commonly referred to as PARylation and MARylation, respectively[ 120 , 121 ]. These modifications regulate a myriad of cellular processes, including DNA damage response, unfolded protein response, cell cycle progression, cell death, metabolism, and immune responses[ 122 - 125 ]. Enzymes in both mammals and microbes can attach, erase, or recognize ADP-ribosyl moieties of target proteins[ 126 ].…”

Literary Identification of Differentially Hydroxymethylated DNA Regions for Type 2 Diabetes Mellitus: A Scoping Minireview

“…Zampieri et al [22] investigated differences in PARylation levels (PAR) and DNA hydroxymethylation status in peripheral blood mononuclear cells between 61 T2DM subjects (who were further stratified into low PAR and high PAR subjects) vs. 48 controls in an age-and gender-matched case-control study. Poly(ADP)-ribosylation (PARylation) was a post-translational protein modification process catalyzed by the poly(ADP-ribose) polymerase (PARP) enzymes and played a role in DNA damage and repair [32]. As illustrated in a previously published review by this research group [33], PARylation controls DNA methylation patterns.…”

The Role of Poly(ADP-ribose) Polymerase 1 in Nuclear and Mitochondrial Base Excision Repair

“…The DNA damage response PARPs, PARPs 1–3, are the most well-known. PARP-1 generates the majority of intracellular PARylation (~90%) [ 17 ]. PARP-1 and PARP-2 play important roles in embryonic development and a PARP-1/PARP-2 double knockout is lethal, causing death at gastrulation [ 18 ].…”