scholarly journals Mitotic spindle disassembly occurs via distinct subprocesses driven by the anaphase-promoting complex, Aurora B kinase, and kinesin-8

2010 ◽  
Vol 191 (4) ◽  
pp. 795-808 ◽  
Author(s):  
Jeffrey B. Woodruff ◽  
David G. Drubin ◽  
Georjana Barnes
Keyword(s):  
Mitotic Spindle ◽  
Cell Cycle Progression ◽  
Dynamic Structure ◽  
Aurora B ◽  
Anaphase Promoting Complex ◽  
Microtubule Depolymerization ◽  
Aurora B Kinase ◽  
Synthetic Lethal ◽  
Spindle Disassembly ◽  
Spindle Elongation

The mitotic spindle is a complex and dynamic structure. Although much has been learned about how spindles assemble and mediate chromosome segregation, how spindles rapidly and irreversibly disassemble during telophase is less clear. We used synthetic lethal screens in budding yeast to identify mutants defective in spindle disassembly. Real-time, live cell imaging analysis of spindle disassembly was performed on nine mutants defective in this process. Results of this analysis suggest that spindle disassembly is achieved by mechanistically distinct but functionally overlapping subprocesses: disengagement of the spindle halves, arrest of spindle elongation, and initiation of interpolar microtubule depolymerization. These subprocesses are largely governed by the anaphase-promoting complex, Aurora B kinase, and kinesin-8. Combinatorial inhibition of these subprocesses yielded cells with hyperstable spindle remnants and dramatic defects in cell cycle progression, establishing that rapid spindle disassembly is crucial for cell proliferation.

scholarly journals Cdc14-regulated midzone assembly controls anaphase B

2007 ◽  
Vol 177 (6) ◽  
pp. 981-993 ◽  
Author(s):  
Anton Khmelinskii ◽  
Clare Lawrence ◽  
Johanna Roostalu ◽  
Elmar Schiebel
Keyword(s):  
Cell Cycle ◽  
Protein Phosphatase ◽  
Cross Linking ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Spindle Midzone ◽  
A Cell ◽  
Spindle Elongation ◽  
And Function ◽  
Anaphase B

Spindle elongation in anaphase of mitosis is a cell cycle–regulated process that requires coordination between polymerization, cross-linking, and sliding of microtubules (MTs). Proteins that assemble at the spindle midzone may be important for this process. In this study, we show that Ase1 and the separase–Slk19 complex drive midzone assembly in yeast. Whereas the conserved MT-bundling protein Ase1 establishes a midzone, separase–Slk19 is required to focus and center midzone components. An important step leading to spindle midzone assembly is the dephosphorylation of Ase1 by the protein phosphatase Cdc14 at the beginning of anaphase. Failure to dephosphorylate Ase1 delocalizes midzone proteins and delays the second, slower phase of anaphase B. In contrast, in cells expressing nonphosphorylated Ase1, anaphase spindle extension is faster, and spindles frequently break. Cdc14 also controls the separase–Slk19 complex indirectly via the Aurora B kinase. Thus, Cdc14 regulates spindle midzone assembly and function directly through Ase1 and indirectly via the separase–Slk19 complex.

Recombinant expression, reconstitution and structure of human anaphase-promoting complex (APC/C)

2012 ◽  
Vol 449 (2) ◽  
pp. 365-371 ◽  
Author(s):  
Ziguo Zhang ◽  
Jing Yang ◽  
Eric H. Kong ◽  
William C. H. Chao ◽  
Edward P. Morris ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Recombinant Expression ◽  
Three Dimensional ◽  
Homology Model ◽  
Particle Analysis ◽  
Anaphase Promoting Complex ◽  
Cycle Progression ◽  
Synthetic Lethal ◽  
Dimensional Reconstruction ◽  
A Subunit

Mechanistic and structural studies of large multi-subunit assemblies are greatly facilitated by their reconstitution in heterologous recombinant systems. In the present paper, we describe the generation of recombinant human APC/C (anaphase-promoting complex/cyclosome), an E3 ubiquitin ligase that regulates cell-cycle progression. Human APC/C is composed of 14 distinct proteins that assemble into a complex of at least 19 subunits with a combined molecular mass of ~1.2 MDa. We show that recombinant human APC/C is correctly assembled, as judged by its capacity to ubiquitinate the budding yeast APC/C substrate Hsl1 (histone synthetic lethal 1) dependent on the APC/C co-activator Cdh1 [Cdc (cell division cycle) 20 homologue 1], and its three-dimensional reconstruction by electron microscopy and single-particle analysis. Successful reconstitution validates the subunit composition of human APC/C. The structure of human APC/C is compatible with the Saccharomyces cerevisiae APC/C homology model, and in contrast with endogenous human APC/C, no evidence for conformational flexibility of the TPR (tetratricopeptide repeat) lobe is observed. Additional density present in the human APC/C structure, proximal to Apc3/Cdc27 of the TPR lobe, is assigned to the TPR subunit Apc7, a subunit specific to vertebrate APC/C.

scholarly journals Identification of a Mid-anaphase Checkpoint in Budding Yeast

1997 ◽  
Vol 136 (2) ◽  
pp. 345-354 ◽  
Author(s):  
Sam S. Yang ◽  
Elaine Yeh ◽  
E.D. Salmon ◽  
Kerry Bloom
Keyword(s):  
Mitotic Spindle ◽  
Cellular Response ◽  
Cell Cycle Progression ◽  
Time Lapse ◽  
Physical Distance ◽  
Cycle Progression ◽  
Contrast Analysis ◽  
Spindle Elongation ◽  
Chromosome Integrity ◽  
Anaphase B

Activation of a facultative, dicentric chromosome provides a unique opportunity to introduce a double strand DNA break into a chromosome at mitosis. Time lapse video enhanced-differential interference contrast analysis of the cellular response upon dicentric activation reveals that the majority of cells initiates anaphase B, characterized by pole–pole separation, and pauses in mid-anaphase for 30–120 min with spindles spanning the neck of the bud before completing spindle elongation and cytokinesis. The length of the spindle at the delay point (3–4 μm) is not dependent on the physical distance between the two centromeres, indicating that the arrest represents surveillance of a dicentric induced aberration. No mid-anaphase delay is observed in the absence of the RAD9 checkpoint gene, which prevents cell cycle progression in the presence of damaged DNA. These observations reveal RAD9- dependent events well past the G2/M boundary and have considerable implications in understanding how chromosome integrity and the position and state of the mitotic spindle are monitored before cytokinesis.

scholarly journals Ipl1/Aurora B kinase coordinates synaptonemal complex disassembly with cell cycle progression and crossover formation in budding yeast meiosis

2009 ◽  
Vol 23 (18) ◽  
pp. 2237-2251 ◽  
Author(s):  
P. Jordan ◽  
A. Copsey ◽  
L. Newnham ◽  
E. Kolar ◽  
M. Lichten ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Synaptonemal Complex ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Cycle Progression ◽  
Yeast Meiosis

Regulation of kinetochore–microtubule attachments by Aurora B kinase

2009 ◽  
Vol 37 (5) ◽  
pp. 976-980 ◽  
Author(s):  
Dan Liu ◽  
Michael A. Lampson
Keyword(s):  
Opposite Direction ◽  
Mitotic Spindle ◽  
Present Review ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Spindle Microtubules ◽  
Segregation Of Chromosomes

Accurate segregation of chromosomes in mitosis requires that spindle microtubules attach sister kinetochores to opposite poles of the mitotic spindle (biorientation). To achieve biorientation of all chromosomes, incorrect attachments are selectively destabilized, providing a fresh opportunity to biorient, whereas correct attachments are stabilized. Tension across the centromere may be the signal that distinguishes different attachment states, as spindle microtubules pull bioriented sister kinetochores in the opposite direction. Destabilization of incorrect attachments requires the Ipl1/Aurora B kinase, which phosphorylates kinetochore substrates that directly interact with microtubules. The present review focuses on how Aurora B regulates attachments in response to centromere tension.

scholarly journals RecQL4-Aurora B kinase axis is essential for cellular proliferation, cell cycle progression, and mitotic integrity

Oncogenesis ◽  
2018 ◽  
Vol 7 (9) ◽  
Author(s):  
Hongbo Fang ◽  
Kaifeng Niu ◽  
Dongliang Mo ◽  
Yuqi Zhu ◽  
Qunsong Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cellular Proliferation ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Cycle Progression

Aurora B kinase is required for cell cycle progression in silkworm

Gene ◽  
2017 ◽  
Vol 599 ◽  
pp. 60-67 ◽  
Author(s):  
Xiaoxu Gang ◽  
Wenliang Qian ◽  
Tianlei Zhang ◽  
Xinxin Yang ◽  
Qingyou Xia ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Cycle Progression

scholarly journals A TPR domain–containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B

2013 ◽  
Vol 201 (2) ◽  
pp. 217-231 ◽  
Author(s):  
Wilco Nijenhuis ◽  
Eleonore von Castelmur ◽  
Dene Littler ◽  
Valeria De Marco ◽  
Eelco Tromer ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Cell Cycle Progression ◽  
Mitotic Checkpoint ◽  
Binding Activity ◽  
Tetratricopeptide Repeat ◽  
Aurora B ◽  
Calponin Homology Domain ◽  
Cycle Progression ◽  
Tpr Domain

The mitotic checkpoint ensures correct chromosome segregation by delaying cell cycle progression until all kinetochores have attached to the mitotic spindle. In this paper, we show that the mitotic checkpoint kinase MPS1 contains an N-terminal localization module, organized in an N-terminal extension (NTE) and a tetratricopeptide repeat (TPR) domain, for which we have determined the crystal structure. Although the module was necessary for kinetochore localization of MPS1 and essential for the mitotic checkpoint, the predominant kinetochore binding activity resided within the NTE. MPS1 localization further required HEC1 and Aurora B activity. We show that MPS1 localization to kinetochores depended on the calponin homology domain of HEC1 but not on Aurora B–dependent phosphorylation of the HEC1 tail. Rather, the TPR domain was the critical mediator of Aurora B control over MPS1 localization, as its deletion rendered MPS1 localization insensitive to Aurora B inhibition. These data are consistent with a model in which Aurora B activity relieves a TPR-dependent inhibitory constraint on MPS1 localization.

scholarly journals Overlapping kinetochore targets of CK2 and Aurora B kinases in mitotic regulation

2011 ◽  
Vol 22 (15) ◽  
pp. 2680-2689 ◽  
Author(s):  
Yutian Peng ◽  
Catherine C. L. Wong ◽  
Yuko Nakajima ◽  
Randall G. Tyers ◽  
Ali S. Sarkeshik ◽  
...  
Keyword(s):  
Protein Kinase Ck2 ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Aurora B ◽  
Cycle Progression ◽  
Spindle Microtubules ◽  
Spindle Elongation ◽  
Mitotic Regulation ◽  
Kinase Ck2 ◽  
Kinetochore Function

Protein kinase CK2 is one of the most conserved kinases in eukaryotic cells and plays essential roles in diverse processes. While we know that CK2 plays a role(s) in cell division, our understanding of how CK2 regulates cell cycle progression is limited. In this study, we revealed a regulatory role for CK2 in kinetochore function. The kinetochore is a multi-protein complex that assembles on the centromere of a chromosome and functions to attach chromosomes to spindle microtubules. To faithfully segregate chromosomes and maintain genomic integrity, the kinetochore is tightly regulated by multiple mechanisms, including phosphorylation by Aurora B kinase. We found that a loss of CK2 kinase activity inhibits anaphase spindle elongation and results in chromosome missegregation. Moreover, a lack of CK2 activates the spindle assembly checkpoint. We demonstrate that CK2 associates with Mif2, the Saccharomyces cerevisiae homologue of human CENP-C, which serves as an important link between the inner and outer kinetochore. Furthermore, we show Mif2 and the inner kinetochore protein Ndc10 are phosphorylated by CK2, and this phosphorylation plays antagonistic and synergistic roles with Aurora B phosphorylation of these targets, respectively.

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