Preserving the genome by regulating chromatin association with the nuclear envelope

The nuclear envelope compartmentalizes chromatin within eukaryotic cells and influences diverse cellular functions by controlling nucleocytoplasmic trafficking. Recent evidence has revealed the importance of interactions between chromatin and nuclear envelope components in the maintenance of genome integrity. Nuclear pore complexes (NPCs), traditionally regarded as transport gateways, have emerged as specialized hubs involved in organizing genome architecture, influencing DNA topology, and modulating DNA repair. Here, we review the interplay between the nuclear envelope, chromatin and DNA damage checkpoint pathways, and discuss the physiological and pathological implications of these associations.