scholarly journals Tension-Induced Error Correction and Not Kinetochore Attachment Status Activates the SAC in an Aurora-B/C-Dependent Manner in Oocytes

2018 ◽  
Vol 28 (1) ◽  
pp. 130-139.e3 ◽  
Author(s):  
Antoine Vallot ◽  
Ioanna Leontiou ◽  
Damien Cladière ◽  
Warif El Yakoubi ◽  
Susanne Bolte ◽  
...  
Keyword(s):  
Error Correction ◽  
Aurora B ◽  
Dependent Manner

scholarly journals Aurora B kinase controls the targeting of the Astrin–SKAP complex to bioriented kinetochores

2010 ◽  
Vol 191 (2) ◽  
pp. 269-280 ◽  
Author(s):  
Jens C. Schmidt ◽  
Tomomi Kiyomitsu ◽  
Tetsuya Hori ◽  
Chelsea B. Backer ◽  
Tatsuo Fukagawa ◽  
...  
Keyword(s):  
Error Correction ◽  
Spindle Assembly Checkpoint ◽  
Multiple Roles ◽  
Aurora B ◽  
Dependent Manner ◽  
Dynein Light Chain ◽  
Chromosome Congression ◽  
Chromosome Alignment ◽  
Mitotic Delay ◽  
Associated Proteins

During mitosis, kinetochores play multiple roles to generate interactions with microtubules, and direct chromosome congression, biorientation, error correction, and anaphase segregation. However, it is unclear what changes at the kinetochore facilitate these distinct activities. Here, we describe a complex of the spindle- and kinetochore-associated protein Astrin, the small kinetochore-associated protein (SKAP), and the dynein light chain LC8. Although most dynein-associated proteins localize to unaligned kinetochores in an Aurora B–dependent manner, Astrin, SKAP, and LC8 localization is antagonized by Aurora B such that they target exclusively to bioriented kinetochores. Astrin–SKAP-depleted cells fail to maintain proper chromosome alignment, resulting in a spindle assembly checkpoint–dependent mitotic delay. Consistent with a role in stabilizing bioriented attachments, Astrin and SKAP bind directly to microtubules and are required for CLASP localization to kinetochores. In total, our results suggest that tension-dependent Aurora B phosphorylation can act to control outer kinetochore composition to provide distinct activities to prometaphase and metaphase kinetochores.

scholarly journals Chromosome instability in tumor cells due to defects in Aurora B mediated error correction at kinetochores

Cell Cycle ◽  
2018 ◽  
Vol 17 (23) ◽  
pp. 2622-2636 ◽  
Author(s):  
Haomin Huang ◽  
Michael Lampson ◽  
Andrey Efimov ◽  
Timothy J. Yen
Keyword(s):  
Error Correction ◽  
Tumor Cells ◽  
Chromosome Instability ◽  
Aurora B

scholarly journals Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction

2011 ◽  
Vol 30 (8) ◽  
pp. 1508-1519 ◽  
Author(s):  
Stefano Santaguida ◽  
Claudio Vernieri ◽  
Fabrizio Villa ◽  
Andrea Ciliberto ◽  
Andrea Musacchio
Keyword(s):  
Error Correction ◽  
Spindle Checkpoint ◽  
Aurora B

scholarly journals Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Olga Afonso ◽  
Colleen M Castellani ◽  
Liam P Cheeseman ◽  
Jorge G Ferreira ◽  
Bernardo Orr ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Cyclin B1 ◽  
Mitotic Exit ◽  
Aurora B ◽  
Dependent Manner ◽  
Slowing Down ◽  
Molecular Rulers ◽  
Spindle Midzone ◽  
Chromosome Separation ◽  
Chromosome Motion

According to the prevailing ‘clock’ model, chromosome decondensation and nuclear envelope reformation when cells exit mitosis are byproducts of Cdk1 inactivation at the metaphase-anaphase transition, controlled by the spindle assembly checkpoint. However, mitotic exit was recently shown to be a function of chromosome separation during anaphase, assisted by a midzone Aurora B phosphorylation gradient - the ‘ruler’ model. Here we found that Cdk1 remains active during anaphase due to ongoing APC/CCdc20- and APC/CCdh1-mediated degradation of B-type Cyclins in Drosophila and human cells. Failure to degrade B-type Cyclins during anaphase prevented mitotic exit in a Cdk1-dependent manner. Cyclin B1-Cdk1 localized at the spindle midzone in an Aurora B-dependent manner, with incompletely separated chromosomes showing the highest Cdk1 activity. Slowing down anaphase chromosome motion delayed Cyclin B1 degradation and mitotic exit in an Aurora B-dependent manner. Thus, a crosstalk between molecular ‘rulers’ and ‘clocks’ licenses mitotic exit only after proper chromosome separation.

scholarly journals Kinetochore life histories reveal an Aurora-B-dependent error correction mechanism in anaphase

2021 ◽  
Author(s):  
Onur Sen ◽  
Jonathan U. Harrison ◽  
Nigel J. Burroughs ◽  
Andrew D. McAinsh
Keyword(s):  
Error Correction ◽  
Life Histories ◽  
Aurora B ◽  
Error Correction Mechanism ◽  
Dependent Error

TheS. pombeaurora-related kinase Ark1 associates with mitotic structures in a stage dependent manner and is required for chromosome segregation

2001 ◽  
Vol 114 (24) ◽  
pp. 4371-4384 ◽  
Author(s):  
Janni Petersen ◽  
Jeannie Paris ◽  
Martin Willer ◽  
Michel Philippe ◽  
Iain M. Hagan
Keyword(s):  
Fission Yeast ◽  
Histone H3 ◽  
Central Zone ◽  
Chromosome Condensation ◽  
Yeast Cells ◽  
Aurora B ◽  
Dependent Manner ◽  
Aurora A ◽  
Spindle Formation

Metazoans contain three aurora-related kinases. Aurora A is required for spindle formation while aurora B is required for chromosome condensation and cytokinesis. Less is known about the function of aurora C. S. pombe contains a single aurora-related kinase, Ark1. Although Ark1 protein levels remained constant as cells progressed through the mitotic cell cycle, its distribution altered during mitosis and meiosis. Throughout G2 Ark1 was concentrated in one to three nuclear foci that were not associated with the spindle pole body/centromere complex. Following commitment to mitosis Ark1 associated with chromatin and was particularly concentrated at several sites including kinetochores/centromeres. Kinetochore/centromere association diminished during anaphase A, after which it was distributed along the spindle. The protein became restricted to a small central zone that transiently enlarged as the spindle extended. As in many other systems mitotic fission yeast cells exhibit a much greater degree of phosphorylation of serine 10 of histone H3 than interphase cells. A number of studies have linked this modification with chromosome condensation. Ark1 immuno-precipitates phosphorylated serine 10 of histone H3 in vitro. This activity was highest in mitotic extracts. The absence of the histone H3 phospho-serine 10 epitope from mitotic cells in which the ark1+ gene had been deleted (ark1.Δ1); the inability of these cells to resolve their chromosomes during anaphase and the co-localisation of this phospho-epitope with Ark1 early in mitosis, all suggest that Ark1 phosphorylates serine 10 of histone H3 in vivo. ark1.Δ1 cells also exhibited a reduction in kinetochore activity and a minor defect in spindle formation. Thus the enzyme activity, localisation and phenotype arising from our manipulations of this single fission yeast aurora kinase family member suggest that this single kinase is executing functions that are separately implemented by distinct aurora A and aurora B kinases in higher systems.

scholarly journals Elevated polar ejection forces stabilize kinetochore–microtubule attachments

2013 ◽  
Vol 200 (2) ◽  
pp. 203-218 ◽  
Author(s):  
Stuart Cane ◽  
Anna A. Ye ◽  
Sasha J. Luks-Morgan ◽  
Thomas J. Maresca
Keyword(s):  
Molecular Motors ◽  
Molecular Mechanisms ◽  
Critical Force ◽  
Aurora B ◽  
Dependent Manner ◽  
Spindle Poles ◽  
Ejection Force ◽  
Chromosome Alignment ◽  
Directed Motility ◽  
Spindle Microtubules

Chromosome biorientation promotes congression and generates tension that stabilizes kinetochore–microtubule (kt-MT) interactions. Forces produced by molecular motors also contribute to chromosome alignment, but their impact on kt-MT attachment stability is unclear. A critical force that acts on chromosomes is the kinesin-10–dependent polar ejection force (PEF). PEFs are proposed to facilitate congression by pushing chromosomes away from spindle poles, although knowledge of the molecular mechanisms underpinning PEF generation is incomplete. Here, we describe a live-cell PEF assay in which tension was applied to chromosomes by manipulating levels of the chromokinesin NOD (no distributive disjunction; Drosophila melanogaster kinesin-10). NOD stabilized syntelic kt-MT attachments in a dose- and motor-dependent manner by overwhelming the ability of Aurora B to mediate error correction. NOD-coated chromatin stretched away from the pole via lateral and end-on interactions with microtubules, and NOD chimeras with either plus end–directed motility or tip-tracking activity produced PEFs. Thus, kt-MT attachment stability is modulated by PEFs, which can be generated by distinct force-producing interactions between chromosomes and dynamic spindle microtubules.

scholarly journals Excess F-actin mechanically impedes mitosis leading to cytokinesis failure in X-linked neutropenia by exceeding Aurora B kinase error correction capacity

Blood ◽  
2012 ◽  
Vol 120 (18) ◽  
pp. 3803-3811 ◽  
Author(s):  
Dale A. Moulding ◽  
Emad Moeendarbary ◽  
Leo Valon ◽  
Julien Record ◽  
Guillaume T. Charras ◽  
...  
Keyword(s):  
Cell Division ◽  
Error Correction ◽  
Signaling Pathway ◽  
Genomic Instability ◽  
Cell Mechanics ◽  
Aurora B ◽  
Dynamic Events ◽  
Mitotic Abnormalities ◽  
Mechanical Sensors ◽  
Syndrome Protein

Abstract The constitutively active mutant of the Wiskott-Aldrich Syndrome protein (CA-WASp) is the cause of X-linked neutropenia and is linked with genomic instability and myelodysplasia. CA-WASp generates abnormally high levels of cytoplasmic F-actin through dysregulated activation of the Arp2/3 complex leading to defects in cell division. As WASp has no reported role in cell division, we hypothesized that alteration of cell mechanics because of increased F-actin may indirectly disrupt dynamic events during mitosis. Inhibition of the Arp2/3 complex revealed that excess cytoplasmic F-actin caused increased cellular viscosity, slowed all phases of mitosis, and perturbed mitotic mechanics. Comparison of chromosome velocity to the cytoplasmic viscosity revealed that cells compensated for increased viscosity by up-regulating force applied to chromosomes and increased the density of microtubules at kinetochores. Mitotic abnormalities were because of overload of the aurora signaling pathway as subcritical inhibition of Aurora in CA-WASp cells caused increased cytokinesis failure, while overexpression reduced defects. These findings demonstrate that changes in cell mechanics can cause significant mitotic abnormalities leading to genomic instability, and highlight the importance of mechanical sensors such as Aurora B in maintaining the fidelity of hematopoietic cell division.

scholarly journals Phosphorylation of CENP-C by Aurora B facilitates kinetochore attachment error correction in mitosis

2017 ◽  
Vol 114 (50) ◽  
pp. E10667-E10676 ◽  
Author(s):  
Xing Zhou ◽  
Fan Zheng ◽  
Chengliang Wang ◽  
Minhao Wu ◽  
Xiaozhen Zhang ◽  
...  
Keyword(s):  
Error Correction ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Chromosome ◽  
Regulatory Mechanism ◽  
Dynamic Interaction ◽  
Aurora B ◽  
Kinetochore Assembly ◽  
Important Pathway ◽  
Spindle Microtubules

Kinetochores are superprotein complexes that orchestrate chromosome segregation via a dynamic interaction with spindle microtubules. A physical connection between CENP-C and the Mis12–Ndc80–Knl1 (KMN) protein network is an important pathway that is used to assemble kinetochores on CENP-A nucleosomes. Multiple outer kinetochore components are phosphorylated by Aurora B kinase to activate the spindle assembly checkpoint (SAC) and to ensure accurate chromosome segregation. However, it is unknown whether Aurora B can phosphorylate inner kinetochore components to facilitate proper mitotic chromosome segregation. Here, we reported the structure of the fission yeast Schizosaccharomyces pombe Mis12–Nnf1 complex and showed that N-terminal residues 26–50 in Cnp3 (the CENP-C homolog of S. pombe) are responsible for interacting with the Mis12 complex. Interestingly, Thr28 of Cnp3 is a substrate of Ark1 (the Aurora B homolog of S. pombe), and phosphorylation impairs the interaction between the Cnp3 and Mis12 complex. The expression of a phosphorylation-mimicking Cnp3 mutant results in defective chromosome segregation due to improper kinetochore assembly. These results establish a previously uncharacterized regulatory mechanism involved in CENP-C–Mis12-facilitated kinetochore attachment error correction to ensure accurate chromosome segregation during mitosis.

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