Nup2 requires a highly divergent partner, NupA, to fulfill functions at nuclear pore complexes and the mitotic chromatin region.
Bottom Line: These mitotic problems are not caused by overall defects in mitotic NPC disassembly-reassembly or general nuclear import.However, without Nup2 or NupA, although the SAC protein Mad1 locates to its mitotic locations, it fails to locate to NPCs normally in G1 after mitosis.Collectively the study provides new insight into the roles of Nup2 and NupA during mitosis and in a surveillance mechanism that regulates nucleokinesis when mitotic defects occur after SAC fulfillment.
Affiliation: Laboratory of Gene Regulation and Development, National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.Show MeSH
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Mentions: In cells lacking Nup2 or NupA, although the SAC is engaged causing mitotic delay, the cells do not all subsequently complete mitosis normally, even though the SAC is apparently fulfilled to allow progression into anaphase. This was revealed by monitoring formation of daughter nuclei in ΔnupA cells using the inner nuclear membrane (INM) marker AN0162-GFP in combination with NLS-DsRed. AN0162 is an INM marker that contains a C-terminal transmembrane domain and is similar to the Schizosaccharomyces pombe INM protein Bqt4 (unpublished data and annotated at AspGD as AN0162). During karyokinesis, the NE undergoes double restrictions and abscissions to generate daughter nuclei. This process also separates the nucleolus from nuclei (Ukil et al., 2009). Twenty percent of nupA- nuclei displayed defects during mitotic exit, and although two apparently normal G1 nuclei were initially formed, they remain associated via the NE, and karyokinesis failed, resulting in the formation of a single diploid nucleus (Figure 7, B and E). During failed nucleokinesis, AN0162 did not locate correctly around the nucleolus (compare Figure 7, A and B, arrow). Furthermore, after several rounds of mitosis, some mutant polyploid nuclei were seen to form multiple bipolar spindles during mitosis (Figure 7D), indicating that these nuclei were the products of more than one round of defective karyokinesis. Lack of Nup2 or NupA therefore compromises aspects of mitosis that are monitored by the SAC and also perturbs NE dynamics during mitotic exit, which can lead to failed karyokinesis.
Affiliation: Laboratory of Gene Regulation and Development, National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.