PARylation at the Genome-Proteome Interface: Regulation of DNA Repair Protein Dynamics.

Poly(ADP-ribosyl)ation (PARylation) is a rapid, reversible DNA damage response that promotes chromatin remodeling and the recruitment of repair factors. Genome maintenance also involves regulating the assembly, chromatin residence, exchange, and disengagement of repair proteins after lesion processing. This review examines PARylation through the lens of repair protein dynamics, distinguishing direct poly(ADP-ribose) (PAR)-dependent regulation from PAR-associated events and broader nuclear protein quality-control pathways. The strongest evidence concerns recruitment and chromatin residence. PAR binding drives XRCC1 accumulation at base excision repair (BER) and single-strand break (SSB) intermediates. In contrast, auto-PARylation promotes PARP1 release, and PARP inhibition favors persistent PARP1-DNA complexes that may require SUMO-RNF4-UFD1-p97/VCP-dependent extraction. In nucleotide excision repair (NER), PARP1-associated DDB2 regulation, ALC1 recruitment, and chromatin remodeling intersect with ubiquitin-dependent DDB2-XPC exchange. PAR-dependent condensation may add a spatial layer of protein organization, although its contribution remains context-dependent. We further discuss implications for PARP- and PARG-directed therapy and research-stage functional readouts. Together, these observations define a testable proteostatic-rheostat framework in which variable PAR signals influence the recruitment of selected repair proteins and subsequent chromatin residence; meanwhile, later extraction and turnover involve distinct, intersecting quality-control mechanisms.