scholarly journals Regulation of Mitotic Spindle Asymmetry by SUMO and the Spindle-Assembly Checkpoint in Yeast

2008 ◽  
Vol 18 (16) ◽  
pp. 1249-1255 ◽  
Author(s):  
Christian Leisner ◽  
Daniel Kammerer ◽  
Annina Denoth ◽  
Mirjam Britschi ◽  
Yves Barral ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly

scholarly journals Synergistic role of fission yeast Alp16GCP6 and Mzt1MOZART1 in γ-tubulin complex recruitment to mitotic spindle pole bodies and spindle assembly

2016 ◽  
Vol 27 (11) ◽  
pp. 1753-1763 ◽  
Author(s):  
Hirohisa Masuda ◽  
Takashi Toda
Keyword(s):  
Fission Yeast ◽  
Mitotic Spindle ◽  
Spindle Assembly Checkpoint ◽  
Synthetic Lethality ◽  
Spindle Assembly ◽  
Spindle Pole ◽  
Microtubule Assembly ◽  
Spindle Microtubule ◽  
Spindle Pole Bodies ◽  
Mitotic Spindle Pole

In fission yeast, γ-tubulin ring complex (γTuRC)–specific components Gfh1GCP4, Mod21GCP5, and Alp16GCP6 are nonessential for cell growth. Of these deletion mutants, only alp16Δ shows synthetic lethality with temperature-sensitive mutants of Mzt1MOZART1, a component of the γTuRC required for recruitment of the complex to microtubule-organizing centers. γ-Tubulin small complex levels at mitotic spindle pole bodies (SPBs, the centrosome equivalent in fungi) and microtubule levels for preanaphase spindles are significantly reduced in alp16Δ cells but not in gfh1Δ or mod21Δ cells. Furthermore, alp16Δ cells often form monopolar spindles and frequently lose a minichromosome when the spindle assembly checkpoint is inactivated. Alp16GCP6 promotes Mzt1-dependent γTuRC recruitment to mitotic SPBs and enhances spindle microtubule assembly in a manner dependent on its expression levels. Gfh1GCP4 and Mod21GCP5 are not required for Alp16GCP6-dependent γTuRC recruitment. Mzt1 has an additional role in the activation of the γTuRC for spindle microtubule assembly. The ratio of Mzt1 to γTuRC levels for preanaphase spindles is higher than at other stages of the cell cycle. Mzt1 overproduction enhances spindle microtubule assembly without affecting γTuRC levels at mitotic SPBs. We propose that Alp16GCP6 and Mzt1 act synergistically for efficient bipolar spindle assembly to ensure faithful chromosome segregation.

scholarly journals Interactions between N-Terminal Modules in MPS1 Enable Spindle Checkpoint Silencing

2018 ◽  
Author(s):  
Spyridon T. Pachis ◽  
Yoshitaka Hiruma ◽  
Anastassis Perrakis ◽  
Geert J.P.L. Kops
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Intramolecular Interactions ◽  
Mitotic Progression ◽  
Microtubule Attachment ◽  
Anaphase Onset ◽  
Regulatory Input ◽  
Tpr Domain

ABSTRACTFaithful chromosome segregation relies on the ability of the spindle assembly checkpoint (SAC) to delay anaphase onset until all chromosomes are attached to the mitotic spindle via their kinetochores. MPS1 kinase is recruited to unattached kinetochores to initiate SAC signaling, and is removed from kinetochores once stable microtubule attachments have been formed to allow normal mitotic progression. Here we show that a helical fragment within the kinetochore-targeting NTE module of MPS1 is required for interactions with kinetochores, and also forms intramolecular interactions with its adjacent TPR domain. Bypassing this NTE-TPR interaction results in high MPS1 levels at kinetochores due to loss of regulatory input into MPS1 localization, ineffecient MPS1 delocalization from kinetochores upon microtubule attachment, and SAC silencing defects. These results show that SAC responsiveness to attachments relies on regulated intramolecular interactions in MPS1 and highlight the sensitivity of mitosis to perturbations in the dynamics of the MSP1-NDC80-C interactions.

scholarly journals Intrakinetochore stretch is associated with changes in kinetochore phosphorylation and spindle assembly checkpoint activity

2009 ◽  
Vol 184 (3) ◽  
pp. 373-381 ◽  
Author(s):  
Thomas J. Maresca ◽  
Edward D. Salmon
Keyword(s):  
Drosophila Melanogaster ◽  
Green Fluorescent Protein ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Spindle Assembly Checkpoint ◽  
Fluorescent Protein ◽  
Spindle Assembly ◽  
Centromeric Chromatin ◽  
Cell Assays ◽  
Green Fluorescent

Cells have evolved a signaling pathway called the spindle assembly checkpoint (SAC) to increase the fidelity of chromosome segregation by generating a “wait anaphase” signal until all chromosomes are properly aligned within the mitotic spindle. It has been proposed that tension generated by the stretch of the centromeric chromatin of bioriented chromosomes stabilizes kinetochore microtubule attachments and turns off SAC activity. Although biorientation clearly causes stretching of the centromeric chromatin, it is unclear whether the kinetochore is also stretched. To test whether intrakinetochore stretch occurs and is involved in SAC regulation, we developed a Drosophila melanogaster S2 cell line expressing centromere identifier–mCherry and Ndc80–green fluorescent protein to mark the inner and outer kinetochore domains, respectively. We observed stretching within kinetochores of bioriented chromosomes by monitoring both inter- and intrakinetochore distances in live cell assays. This intrakinetochore stretch is largely independent of a 30-fold variation in centromere stretch. Furthermore, loss of intrakinetochore stretch is associated with enhancement of 3F3/2 phosphorylation and SAC activation.

scholarly journals In-Silico Modeling of the Mitotic Spindle Assembly Checkpoint

PLoS ONE ◽  
2008 ◽  
Vol 3 (2) ◽  
pp. e1555 ◽  
Author(s):  
Bashar Ibrahim ◽  
Stephan Diekmann ◽  
Eberhard Schmitt ◽  
Peter Dittrich
Keyword(s):  
Mitotic Spindle ◽  
In Silico ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
In Silico Modeling ◽  
Mitotic Spindle Assembly

Activation of the Budding Yeast Spindle Assembly Checkpoint Without Mitotic Spindle Disruption

Science ◽  
1996 ◽  
Vol 273 (5277) ◽  
pp. 953-956 ◽  
Author(s):  
K. G. Hardwick ◽  
E. Weiss ◽  
F. C. Luca ◽  
M. Winey ◽  
A. W. Murray
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly Checkpoint ◽  
Budding Yeast ◽  
Spindle Assembly

scholarly journals ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores

2016 ◽  
Vol 212 (6) ◽  
pp. 647-659 ◽  
Author(s):  
Mayumi Isokane ◽  
Thomas Walter ◽  
Robert Mahen ◽  
Bianca Nijmeijer ◽  
Jean-Karim Hériché ◽  
...  
Keyword(s):  
Rna Interference ◽  
Mitotic Spindle ◽  
Spindle Assembly Checkpoint ◽  
Genome Instability ◽  
Quantitative Imaging ◽  
Direct Interaction ◽  
Spindle Assembly ◽  
Mitotic Exit ◽  
Genome Wide ◽  
A Genome

To prevent genome instability, mitotic exit is delayed until all chromosomes are properly attached to the mitotic spindle by the spindle assembly checkpoint (SAC). In this study, we characterized the function of ARHGEF17, identified in a genome-wide RNA interference screen for human mitosis genes. Through a series of quantitative imaging, biochemical, and biophysical experiments, we showed that ARHGEF17 is essential for SAC activity, because it is the major targeting factor that controls localization of the checkpoint kinase Mps1 to the kinetochore. This mitotic function is mediated by direct interaction of the central domain of ARHGEF17 with Mps1, which is autoregulated by the activity of Mps1 kinase, for which ARHGEF17 is a substrate. This mitosis-specific role is independent of ARHGEF17’s RhoGEF activity in interphase. Our study thus assigns a new mitotic function to ARHGEF17 and reveals the molecular mechanism for a key step in SAC establishment.

scholarly journals PRP4 is a spindle assembly checkpoint protein required for MPS1, MAD1, and MAD2 localization to the kinetochores

2007 ◽  
Vol 179 (4) ◽  
pp. 601-609 ◽  
Author(s):  
Emilie Montembault ◽  
Stéphanie Dutertre ◽  
Claude Prigent ◽  
Régis Giet
Keyword(s):  
Rna Processing ◽  
Mitotic Spindle ◽  
Messenger Rna ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Checkpoint Proteins ◽  
Checkpoint Protein ◽  
Anaphase Onset ◽  
Spindle Microtubules ◽  
Spindle Assembly Checkpoint Protein

The spindle checkpoint delays anaphase onset until every chromosome kinetochore has been efficiently captured by the mitotic spindle microtubules. In this study, we report that the human pre–messenger RNA processing 4 (PRP4) protein kinase associates with kinetochores during mitosis. PRP4 depletion by RNA interference induces mitotic acceleration. Moreover, we frequently observe lagging chromatids during anaphase leading to aneuploidy. PRP4-depleted cells do not arrest in mitosis after nocodazole treatment, indicating a spindle assembly checkpoint (SAC) failure. Thus, we find that PRP4 is necessary for recruitment or maintenance of the checkpoint proteins MPS1, MAD1, and MAD2 at the kinetochores. Our data clearly identify PRP4 as a previously unrecognized kinetochore component that is necessary to establish a functional SAC.

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