Importin alpha Characterizes a Micronuclear Environment Associated with Genomic Instability in Human Cancer Cells
Micronuclei (MN) are membrane-enclosed chromatin bodies and hallmarks of genome instability. Here, we show that importin alpha, a key nuclear transport factor, accumulates prominently in a distinct subset of MN in human cultured cells. This selective localization is associated with defective RanGTP-dependent nucleocytoplasmic recycling of importin alpha1 within MN, consistent with reduced RCC1 levels. Live-cell photobleaching revealed remarkably reduced mobility of importin alpha1 between MN and cytoplasm, indicating a collapse of nucleocytoplasmic recycling in this MN subset. Importin alpha1 was also enriched in euchromatin regions and colocalized with chromatin-associated molecules. In contrast, DNA repair and sensing molecules such as RAD51, RPA2, and cGAS showed mutually exclusive localization with importin alpha1 in MN, indicating that MN comprise distinct internal environments. These findings identify importin alpha as a molecular marker of the restricted MN state, representing a microenvironment distinct from subsets characterized by conventional molecular markers of MN. This study provides a new perspective on MN heterogeneity and suggests that importin alpha contributes to genome instability and immune evasion during cancer progression through mechanisms beyond its canonical role in nuclear transport.