2026/01/09 by Molly G. Zych, Maya Contreras, Anna Mammel +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Nuclear Structure and Function #DNA Repair Mechanisms #Microtubule and mitosis dynamics
paper · doi:10.1083/jcb.202510133
Micronuclei (MN), a hallmark of chromosome instability, frequently rupture, leading to protumorigenic consequences. MN rupture requires nuclear lamina defects, yet their underlying causes remain unclear. Here, we demonstrate that MN lamina gaps are linked to excessive MN growth resulting from impaired protein export. This export defect arises from reduced levels of the transport protein RCC1 in MN. Overexpressing RCC1 increases protein export and protects MN from rupture. Differences in RCC1 levels linked to chromatin state also explain why high euchromatin content increases the stability of small MN. Additional RCC1 loss in euchromatic MN results in impaired protein import. For these MN, increasing RCC1, directly or through increasing histone methylation, accelerates rupture. Our findings define a new model of MN rupture, where defects in protein export drives continuous MN growth causing nuclear lamina gaps that predispose MN to membrane rupture and where chromatin-specific features can alter rupture of small MN by further impairing nuclear transport.