Catastrophic nuclear envelope collapse in cancer cell micronuclei

article Catastrophic nuclear envelope collapse in cancer cell micronuclei published yes Emily M. Hatch author Andrew H. Fischer author Thomas J. Deerinck author Martin W HETZER author 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed0000-0002-2111-992X During mitotic exit, missegregated chromosomes can recruit their own nuclear envelope (NE) to form micronuclei (MN). MN have reduced functioning compared to primary nuclei in the same cell, although the two compartments appear to be structurally comparable. Here we show that over 60% of MN undergo an irreversible loss of compartmentalization during interphase due to NE collapse. This disruption of the MN, which is induced by defects in nuclear lamina assembly, drastically reduces nuclear functions and can trigger massive DNA damage. MN disruption is associated with chromatin compaction and invasion of endoplasmic reticulum (ER) tubules into the chromatin. We identified disrupted MN in both major subtypes of human non-small-cell lung cancer, suggesting that disrupted MN could be a useful objective biomarker for genomic instability in solid tumors. Our study shows that NE collapse is a key event underlying MN dysfunction and establishes a link between aberrant NE organization and aneuploidy. Elsevier2013 eng General BiochemistryGenetics and Molecular Biology Cell 0092-8674 2382767410.1016/j.cell.2013.06.007 154147-60 yes E.M. Hatch, A.H. Fischer, T.J. Deerinck, M. Hetzer, Cell 154 (2013) 47–60. Hatch, E. M., Fischer, A. H., Deerinck, T. J., & Hetzer, M. (2013). Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell. Elsevier. <a href="https://doi.org/10.1016/j.cell.2013.06.007">https://doi.org/10.1016/j.cell.2013.06.007</a> Hatch, Emily M., Andrew H. Fischer, Thomas J. Deerinck, and Martin Hetzer. “Catastrophic Nuclear Envelope Collapse in Cancer Cell Micronuclei.” Cell. Elsevier, 2013. <a href="https://doi.org/10.1016/j.cell.2013.06.007">https://doi.org/10.1016/j.cell.2013.06.007</a>. Hatch EM, Fischer AH, Deerinck TJ, Hetzer M. 2013. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell. 154(1), 47–60. E. M. Hatch, A. H. Fischer, T. J. Deerinck, and M. Hetzer, “Catastrophic nuclear envelope collapse in cancer cell micronuclei,” Cell, vol. 154, no. 1. Elsevier, pp. 47–60, 2013. Hatch, Emily M., et al. “Catastrophic Nuclear Envelope Collapse in Cancer Cell Micronuclei.” Cell, vol. 154, no. 1, Elsevier, 2013, pp. 47–60, doi:<a href="https://doi.org/10.1016/j.cell.2013.06.007">10.1016/j.cell.2013.06.007</a>. Hatch EM, Fischer AH, Deerinck TJ, Hetzer M. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell. 2013;154(1):47-60. doi:<a href="https://doi.org/10.1016/j.cell.2013.06.007">10.1016/j.cell.2013.06.007</a> 110852022-04-07T07:50:51Z2024-10-14T11:24:29Z