Base excision repair (BER) and nucleotide excision repair (NER) are traditionally regarded as independent pathways; however, accumulating evidence indicates that ultraviolet (UV)-damaged DNA-binding protein (UV-DDB), a core NER factor, stimulates BER DNA glycosylases, including alkyladenine DNA glycosylase (AAG). Despite this functional link, the molecular basis of the UV-DDB/AAG interaction and its regulation by DNA remain unclear. This study investigated the direct interaction between AAG and UV-DDB using electrophoretic mobility shift assays (EMSA), surface plasmon resonance (SPR), biolayer interferometry (BLI) and AlphaFold3-based structural modeling under DNA-free and DNA-bound conditions. SPR analysis revealed that AAG and UV-DDB form a high-affinity complex in the absence of DNA ($K_D$ ≈ 17.5 nM), which is maintained but reduced approximately 2.6-fold upon binding to apurinic/apyrimidinic site (AP site)-containing dsDNA ($K_D$ ≈ 46.2 nM). BLI analysis independently confirmed this interaction under both DNA-free and DNA-bound conditions, with inter-platform differences consistent with previously reported BLI/SPR variability. EMSA showed UV-DDB-mediated ternary complex formation accompanied by redistribution of binary AAG/DNA species. AlphaFold3 modeling predicted that AAG associates with DDB1 in the DNA-free state, whereas under DNA-bound conditions, DDB2 recognizes the AP site while AAG repositions toward the lesion with multiple active site residues placed in close proximity. These findings support a model in which DNA binding acts as a molecular switch that reconfigures the UV-DDB/AAG interaction, potentially enabling UV-DDB to function as a recruitment platform that facilitates directional progression of AAG through the BER cycle, and providing a structural basis for coordinated integration of BER and NER.

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.