Importin α Characterizes a Micronuclear Environment Associated with Genomic Instability in Human Cancer Cells
Abstract
Micronuclei (MN) are membrane-enclosed chromatin bodies and hallmarks of genome instability. Here, we report that importin α, a key nuclear transport factor, is highly concentrated in a distinct subset of MN in cultured human cancer cells. This selective localization is not governed by classical nuclear transport pathways. Live-cell photobleaching revealed remarkably reduced mobility of importin α between MN and cytoplasm. In addition, the subset of importin α-positive MN exhibited collapsed nuclear envelopes and compromised barrier functions. Importin α was also enriched in euchromatin regions, where it colocalized with chromatin-regulating molecules. Importantly, importin α and DNA repair/sensing molecules such as RAD51, RPA2, and cGAS showed mutually exclusive localization in MN, indicating that MN comprise distinct internal environments. These findings identify importin α as a molecular marker of the restricted MN state, representing a previously unrecognized microenvironment distinct from subsets characterized by conventional molecular markers of disrupted MN. This framework provides new insights into how MN heterogeneity underlies genome instability and immune evasion during cancer progression.
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