Complete ADP-Ribosylation Cycle Inhibitor Cocktail

PAR homeostasis is regulated by the family of PAR polymerases (PARPs) and PARG (Poly (ADP-ribose) glycohydrolase) in response to cellular stress conditions. ADP ribosylation, which is the addition of an ADP-ribose to a protein, is a reversible post-translational modification of proteins mostly involved in the DNA Damage Response (DDR) pathway. Poly-ADP-ribosylation (termed PARylation) is the addition of linear or branched chains of ADP-ribose. PARP and PARG activity are linked to cellular responses in inflammation, ischemia, stroke, and cancer. PARP inhibitors have been used in cancer treatment with success, leading to synthetic lethality when homologous recombination repair (HRR) is already defective. PARG is overexpressed in breast cancer and associated with tumor growth and survival. Decrease in PARG activity can potentiate the effect of current cancer therapies, such as chemotherapy and radiation, making PARG inhibition with selective inhibitors a promising approach in cancer and immunotherapy. Further studies of PARP and PARG will elucidate how the levels of PARylated proteins contribute to disease and can be modulated to provide therapeutic benefit.

If very high ADP-ribosylation cycle activity is expected or present in the cell lysate it is recommended that the cocktail is tested at various concentrations to determine the  optimal concentration to use in your experiment. This cocktail may not target all the ADP-ribose writers and erasers present in cells.