The nuclear pore complex as a spatial organizing hub for high-risk DNA lesions

The nuclear pore complex (NPC) is best known for nucleocytoplasmic transport, but growing evidence implicates nucleoporins and NPC-associated environments in genome maintenance. Here, we discuss the NPC as a spatial organizer of hazardous DNA lesions rather than a passive transport channel. Three functions recur across systems. First, NPC-associated environments can quarantine lesions arising in repetitive DNA, heterochromatin, dysfunctional telomeres, and other high-risk chromatin contexts. Second, nuclear pore association can influence recombination and repair pathway choice. Third, mobile off-pore nucleoporins may act directly at damaged chromatin to stabilize repair-associated chromatin states and restrain harmful RNA-containing intermediates. We distinguish direct mechanistic insight from evidence based on spatial association or genetic perturbation and highlight unresolved questions about NPC heterogeneity, lesion mobility, and protective versus mutagenic repair. This view positions nucleoporins as conditional regulators of genome stability.