Poly adenosine diphosphate ribose (polyADP-ribose or PAR) is a biological molecule composed of repeated units of adenosine diphosphate ribose (ADP-ribose) that are connected by glycosidic bonds. It is synthesized within the cell by the enzyme poly(ADP-ribose) polymerase (PARP) through a process known as poly(ADP-ribosylation).
Poly ADP-ribose plays a crucial role in various cellular processes, particularly in DNA repair, transcription regulation, and maintenance of genomic integrity. It acts as a molecular signal that recruits and activates several proteins involved in these processes. When DNA damage occurs, PARP is activated, leading to the synthesis of polyADP-ribose chains on target proteins, including PARP itself. These chains serve as a scaffold for the recruitment of DNA repair proteins, allowing efficient repair of damaged DNA strands.
In addition to DNA repair, polyADP-ribose is also involved in other cellular functions such as regulating gene expression and cell death pathways. It can modify specific proteins by ADP-ribosylation, influencing their activity, localization, or interaction with other molecules.
Poly ADP-ribose has garnered significant attention in the field of drug discovery due to its importance in cellular processes and its potential as a therapeutic target. Inhibitors of PARP have been developed as anticancer agents, as they selectively target cancer cells with defective DNA repair mechanisms and cause synthetic lethality. Furthermore, modulation of poly ADP-ribose synthesis and degradation has shown promise in various disease states, including neurodegenerative disorders, cardiovascular diseases, and inflammation.
