Liquid‒liquid phase separation and poly(ADP‒ribosyl)ation in the context of ultraviolet radiation-induced stress in mammalian cells.

UNLABELLED

Poly(ADP‒ribose) polymerases (PARPs) consume NAD to synthesize poly(ADP‒ribose) (PAR) primarily via post-translational modification. PAR is degraded mainly by poly (ADP-ribose) glycohydrolase (PARG). PAR can be linear or branched and can have up to 200 monomers. With two phosphates per monomer, PAR is highly negatively charged. PAR can be recognized by specific protein domains and has been described as a "glue" or scaffold for the assembly of multiprotein complexes. PAR is involved in several diverse cellular structures and functions, including DNA replication, transcription, DNA repair, chromatin structure and imprinting regulation, mitotic spindle assembly, cell‒cell junctions, cytoplasmic granule formation, biomineralization and the formation of pathological aggregates. Here, we review the effects of ultraviolet radiation (UVR) on mammalian cells, emphasizing the participation of PAR metabolism in the novel paradigm of liquid‒liquid phase separation (LLPS). Further studies demand interdisciplinary approaches, undoubtedly requiring contributions from biophysicists.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s12551-025-01294-x.