Beyond RNA/DNA: exploring the emerging role of Poly(ADP-ribose): structure, function, and condensate formation

Abstract

Poly(ADP-ribose) (PAR) is an RNA-like homopolymer synthesized by enzymes in response to DNA damage. Increasing evidence indicates that PAR participates in diverse cellular processes, in several cases by promoting or modulating biomolecular condensate formation. While condensate formation has been implicated in a variety of PAR-dependent functions such as DNA repair, stress granule assembly, and chromatin remodeling, the extent to which it is required for specific cellular processes remains an active area of investigation. Serving as a scaffold for intrinsically disordered proteins (IDPs), PAR has been proposed to compete with RNA and DNA to mediate these functions. This review highlights the key differences between PAR and nucleic acids, emphasizing why PAR could be an especially effective scaffold. We compare PAR structures with nucleic acids, and examine the physicochemical factors that influence PAR structure and its condensate formation. Additionally, we highlight the challenges in studying PAR both experimentally and computationally. Finally, we explore PAR’s potential as a drug target, concluding with future research directions aimed at furthering our understanding of its molecular properties, the principles of its condensate formation, and its therapeutic potential.