scholarly journals Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator

2009 ◽  
Vol 184 (5) ◽  
pp. 647-657 ◽  
Author(s):  
Mariana Lince-Faria ◽  
Stefano Maffini ◽  
Bernard Orr ◽  
Yun Ding ◽  
Cláudia Florindo ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Spindle Assembly Checkpoint ◽  
Dynamic Properties ◽  
Nuclear Pore ◽  
Spindle Matrix ◽  
Complex Protein ◽  
Spindle Microtubules ◽  
Spindle Elongation ◽  
Spatiotemporal Control ◽  
Chromosome Motion

A putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible “wait anaphase” signal to the vicinity of the spindle.

scholarly journals Function and Assembly of DNA Looping, Clustering, and Microtubule Attachment Complexes within a Eukaryotic Kinetochore

2009 ◽  
Vol 20 (19) ◽  
pp. 4131-4139 ◽  
Author(s):  
Marybeth Anderson ◽  
Julian Haase ◽  
Elaine Yeh ◽  
Kerry Bloom
Keyword(s):  
Dynamic Properties ◽  
Dna Looping ◽  
Dna Assembly ◽  
Dna Loops ◽  
Microtubule Binding ◽  
Microtubule Attachment ◽  
Histone H3 Variant ◽  
Complex Protein ◽  
Mechanical Linkage ◽  
Spindle Microtubules

The kinetochore is a complex protein–DNA assembly that provides the mechanical linkage between microtubules and the centromere DNA of each chromosome. Centromere DNA in all eukaryotes is wrapped around a unique nucleosome that contains the histone H3 variant CENP-A (Cse4p in Saccharomyces cerevisiae). Here, we report that the inner kinetochore complex (CBF3) is required for pericentric DNA looping at the Cse4p-containing nucleosome. DNA within the pericentric loop occupies a spatially confined area that is radially displaced from the interpolar central spindle. Microtubule-binding kinetochore complexes are not involved in pericentric DNA looping but are required for the geometric organization of DNA loops around the spindle microtubules in metaphase. Thus, the mitotic segregation apparatus is a composite structure composed of kinetochore and interpolar microtubules, the kinetochore, and organized pericentric DNA loops. The linkage of microtubule-binding to centromere DNA-looping complexes positions the pericentric chromatin loops and stabilizes the dynamic properties of individual kinetochore complexes in mitosis.

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.

scholarly journals The right place at the right time: Aurora B kinase localization to centromeres and kinetochores

2020 ◽  
Vol 64 (2) ◽  
pp. 299-311 ◽  
Author(s):  
Amanda J. Broad ◽  
Jennifer G. DeLuca
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Protein Complexes ◽  
Centromeric Heterochromatin ◽  
Aurora B ◽  
Mitotic Chromosomes ◽  
Large Protein ◽  
Aurora B Kinase ◽  
Centromeric Protein ◽  
Spindle Microtubules ◽  
The Right

Abstract The fidelity of chromosome segregation during mitosis is intimately linked to the function of kinetochores, which are large protein complexes assembled at sites of centromeric heterochromatin on mitotic chromosomes. These key “orchestrators” of mitosis physically connect chromosomes to spindle microtubules and transduce forces through these connections to congress chromosomes and silence the spindle assembly checkpoint. Kinetochore-microtubule attachments are highly regulated to ensure that incorrect attachments are not prematurely stabilized, but instead released and corrected. The kinase activity of the centromeric protein Aurora B is required for kinetochore-microtubule destabilization during mitosis, but how the kinase acts on outer kinetochore substrates to selectively destabilize immature and erroneous attachments remains debated. Here, we review recent literature that sheds light on how Aurora B kinase is recruited to both centromeres and kinetochores and discuss possible mechanisms for how kinase interactions with substrates at distinct regions of mitotic chromosomes are regulated.

Spatiotemporal control of functional specification and distribution of spindle microtubules with 13, 14 and 15 protofilaments during mitosis in the ciliate Nyctotherus

1985 ◽  
Vol 76 (1) ◽  
pp. 337-355
Author(s):  
U. Eichenlaub-Ritter
Keyword(s):  
Differential Sensitivity ◽  
Microtubule Depolymerization ◽  
Functional Specification ◽  
Microtubule Stability ◽  
Early Anaphase ◽  
Late Telophase ◽  
Spindle Microtubules ◽  
Elongation Phase ◽  
Spatiotemporal Control ◽  
Macronuclear Division

The formation of microtubules with more than 13 protofilaments in the ciliate Nyctotherus ovalis Leidy seems to be a highly ordered process. Such microtubules are restricted to the nucleoplasm and, moreover, to certain stages of nuclear division. They assemble during anaphase of micronuclear mitosis and during the elongation phase of macronuclear division. The number of microtubules with more than 13 protofilaments in the micronuclear nucleoplasm increases as anaphase progresses. Furthermore, assembly of microtubules with 14 and 15 protofilaments seems to proceed concomitantly with net disassembly of 13-protofilament microtubules, because the total amount of polymerized tubulin in the interpolar spindle region remains approximately constant between mid anaphase and late telophase. In addition, evidence for spatial control of the distribution of microtubules with different protofilament numbers in the micronuclear stembody has been found. The percentage of microtubules with 13 protofilaments per stembody cross-section is highest at the ends of the stembody, while the percentage of microtubules with either 14 or 15 protofilaments increases as the middle of the stembody is approached. Temporal control of polymerization of microtubules with high protofilament numbers seems to be exerted independently in the two types of nuclei. For example, when the macronucleus starts to elongate it contains microtubules with more than 13 protofilaments but the metaphase micronucleus still possesses only microtubules with 13 protofilaments at this stage. Control of fidelity of protofilament numbers is not lost in the early stages of micronuclear or macronuclear division when cells are exposed to 2H2O or media containing taxol. Even microtubules that reassemble during recovery of metaphase micronuclei from nocodazole-induced microtubule depolymerization, in either the absence or presence of 2H2O and taxol, possess 13 protofilaments. Similarly, if the introduction of microtubules with 14 and 15 protofilaments is inhibited during early micronuclear anaphase and delayed for 60 min by exposure to nocodazole, such microtubules still assemble during telophase when recovery is permitted. Microtubules that have been assembled under normal conditions show differential sensitivity to nocodazole. During metaphase, nocodazole induces disassembly of most microtubules. There is an increase in microtubule stability that coincides with the appearance of microtubules with high protofilament numbers during early anaphase. However, considerable numbers of 13-protofilament microtubules, as well as microtubules with 14 and 15 protofilaments, exhibit such stability during anaphase.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Chromosome motion and the spindle matrix.

1984 ◽  
Vol 99 (1) ◽  
pp. 137s-143s ◽  
Author(s):  
J Pickett-Heaps ◽  
T Spurck ◽  
D Tippit
Keyword(s):  
Spindle Matrix ◽  
Chromosome Motion

scholarly journals Central-spindle microtubules are strongly coupled to chromosomes during both anaphase A and anaphase B

2019 ◽  
Vol 30 (19) ◽  
pp. 2503-2514 ◽  
Author(s):  
Che-Hang Yu ◽  
Stefanie Redemann ◽  
Hai-Yin Wu ◽  
Robert Kiewisz ◽  
Tae Yeon Yoo ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Tomographic Reconstruction ◽  
Mitotic Spindles ◽  
Strongly Coupled ◽  
Central Spindle ◽  
Spindle Poles ◽  
Meiotic Spindles ◽  
Spindle Microtubules ◽  
Anaphase B ◽  
Chromosome Motion

Spindle microtubules, whose dynamics vary over time and at different locations, cooperatively drive chromosome segregation. Measurements of microtubule dynamics and spindle ultrastructure can provide insight into the behaviors of microtubules, helping elucidate the mechanism of chromosome segregation. Much work has focused on the dynamics and organization of kinetochore microtubules, that is, on the region between chromosomes and poles. In comparison, microtubules in the central-spindle region, between segregating chromosomes, have been less thoroughly characterized. Here, we report measurements of the movement of central-spindle microtubules during chromosome segregation in human mitotic spindles and Caenorhabditis elegans mitotic and female meiotic spindles. We found that these central-spindle microtubules slide apart at the same speed as chromosomes, even as chromosomes move toward spindle poles. In these systems, damaging central-spindle microtubules by laser ablation caused an immediate and complete cessation of chromosome motion, suggesting a strong coupling between central-spindle microtubules and chromosomes. Electron tomographic reconstruction revealed that the analyzed anaphase spindles all contain microtubules with both ends between segregating chromosomes. Our results provide new dynamical, functional, and ultrastructural characterizations of central-spindle microtubules during chromosome segregation in diverse spindles and suggest that central-spindle microtubules and chromosomes are strongly coupled in anaphase.

scholarly journals ConnectingGCN5’s centromeric SAGA to the mitotic tension-sensing checkpoint

2018 ◽  
Vol 29 (18) ◽  
pp. 2201-2212 ◽  
Author(s):  
Emily L. Petty ◽  
Masha Evpak ◽  
Lorraine Pillus
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Spindle Assembly Checkpoint ◽  
Binding Function ◽  
Chromatid Cohesion ◽  
Histone H3 Variant ◽  
Spindle Microtubules ◽  
Low Tension ◽  
Centromere Histone H3 ◽  
Segregation Of Chromosomes

Multiple interdependent mechanisms ensure faithful segregation of chromosomes during cell division. Among these, the spindle assembly checkpoint monitors attachment of spindle microtubules to the centromere of each chromosome, whereas the tension-sensing checkpoint monitors the opposing forces between sister chromatid centromeres for proper biorientation. We report here a new function for the deeply conserved Gcn5 acetyltransferase in the centromeric localization of Rts1, a key player in the tension-sensing checkpoint. Rts1 is a regulatory component of protein phopshatase 2A, a near universal phosphatase complex, which is recruited to centromeres by the Shugoshin (Sgo) checkpoint component under low-tension conditions to maintain sister chromatid cohesion. We report that loss of Gcn5 disrupts centromeric localization of Rts1. Increased RTS1 dosage robustly suppresses gcn5∆ cell cycle and chromosome segregation defects, including restoration of Rts1 to centromeres. Sgo1’s Rts1-binding function also plays a key role in RTS1 dosage suppression of gcn5∆ phenotypes. Notably, we have identified residues of the centromere histone H3 variant Cse4 that function in these chromosome segregation-related roles of RTS1. Together, these findings expand the understanding of the mechanistic roles of Gcn5 and Cse4 in chromosome segregation.

Chromator, a novel and essential chromodomain protein interacts directly with the putative spindle matrix protein skeletor

2004 ◽  
Vol 93 (5) ◽  
pp. 1033-1047 ◽  
Author(s):  
Uttama Rath ◽  
Dong Wang ◽  
Yun Ding ◽  
Ying-Zhi Xu ◽  
Hongying Qi ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Spindle Matrix
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