A Last-Minute Rescue of Trapped Chromatin

University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, MA 01655, USA.
Cell (Impact Factor: 32.24). 03/2009; 136(3):397-9. DOI: 10.1016/j.cell.2009.01.028
Source: PubMed


Chromosome segregation and cytokinesis must be tightly coordinated to ensure that chromosomes are accurately partitioned between dividing cells. In this issue, Steigemann et al. (2009) report that Aurora B kinase promotes proper chromosome segregation by delaying abscission when chromatin is trapped between dividing cells.

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    • "Polyploid nuclei generated via the karyokinesis checkpoint can therefore contribute to cell growth and could also potentially undergo reductional mitotic division to regenerate correct ploidy, as previously seen after microtubule poison washout in A. nidulans (De Souza et al., 2011). The karyokinesis checkpoint has similarities with the Aurora B– mediated abscission checkpoint (NoCut pathway in budding yeast), which prevents aneuploidy by causing delays in cytokinesis if chromatin becomes trapped between daughter cells (Norden et al., 2006; Chen and Doxsey, 2009; Steigemann and Gerlich, 2009; Steigemann et al., 2009). However, in the early stages of A. nidulans growth, cytokinesis is not linked to mitosis (Clutterbuck, 1970; Harris et al., 1994), and so cytokinesis cannot be a target of checkpoints involved in maintaining ploidy when mitotic DNA is slow to segregate . "
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    ABSTRACT: Chromatin and nuclear pore complexes (NPCs) undergo dramatic changes during mitosis which in vertebrates and Aspergillus nidulans involves movement of Nup2 from NPCs to the chromatin region to fulfill unknown functions. This transition is shown to require the Cdk1 mitotic kinase and to be promoted prematurely by ectopic expression of the NIMA kinase. Nup2 localizes with a copurifying partner termed NupA, a highly divergent yet essential NPC protein. NupA and Nup2 locate throughout the chromatin region during prophase but during anaphase move to surround segregating DNA. NupA function is shown to involve targeting Nup2 to its interphase and mitotic locations. Deletion of either Nup2 or NupA causes identical mitotic defects that initiate a spindle assembly checkpoint (SAC) dependent mitotic delay and also cause defects in karyokinesis. These mitotic problems are not caused either 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 to the roles of Nup2 and NupA during mitosis and in a surveillance mechanism that regulates nucleokinesis when mitotic defects occur after SAC fulfillment. © 2014 by The American Society for Cell Biology.
    Preview · Article · Dec 2014 · Molecular Biology of the Cell
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    ABSTRACT: Eukaryotic cell division is an orderly and timely process involving the error-free segregation of chromosomes and cytoplasmic components to give rise to two separate daughter cells. Defects in genome maintenance mechanisms such as cell cycle checkpoints and DNA repair can impact the segregation of the genome during mitosis leading to multiple chromosomal imbalances. In mammals, the DNA damage checkpoint effector Checkpoint Kinase 1 (Chk1) is essential for responses to DNA replication errors, external DNA damage, and chromatin breaks. We reported recently that Chk1 also was essential for chromosome segregation and completion of cytokinesis to prevent genomic instability. Our studies demonstrated that Chk1 deficiency in mitotic cells causes chromosome mis-alignment, lagging chromosomes, chromosome mis-segregation, cytokinetic regression and binucleation. In addition, abrogation of Chk1 resulted in aberrant localization of mitotic Aurora B kinase at the metaphase plate, anaphase spindle midzone, and cytokinetic midbody as studied both in various cell lines and in a mouse model. Therefore, inappropriate regulation of Chk1 levels during cell cycle progression will result in failed cell division and enhanced genomic instability.
    Full-text · Article · Sep 2009 · Cell cycle (Georgetown, Tex.)
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    ABSTRACT: Aurora B is critically involved in ensuring proper cytokinesis and maintaining genomic stability. The tumor suppressor RASSF1A regulates cell cycle progression by regulating mitotic progression, G(1)-S transition, and microtubule stability. We previously reported that both Aurora A and Aurora B phosphorylate RASSF1A, and showed that phosphorylation of RASSF1A by Aurora A blocks the inhibitory function of RASSF1A toward anaphase-promoting complex-Cdc20. However, the role of Aurora B-mediated RASSF1A phosphorylation remains unknown. Here, we show that phosphorylation of RASSF1A on Ser203 by Aurora B during late mitosis has a critical role in regulating cytokinesis. Notably, RASSF1A interacts with Syntaxin16, a member of the t-SNARE family, at the midzone and midbody during late mitosis. Aurora B is required for this interaction and for the subsequent recruitment of Syntaxin16 to the midzone and midbody, a prerequisite for the successful completion of cytokinesis. Furthermore, Aurora B depletion results in a failure of Syntaxin16 to properly localize to the midzone and midbody, a mislocalization that was prevented by overexpression of the phosphomimetic RASSF1A (S203D) mutant. Finally, either depletion of Syntaxin16 or expression of the nonphosphorylatable RASSF1A (S203A) mutant results in cytokinesis defects. Our findings implicate Aurora B-mediated phosphorylation of RASSF1A in the regulation of cytokinesis.
    No preview · Article · Nov 2009 · Cancer Research
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