scholarly journals Kinetochores accelerate centrosome separation to ensure faithful chromosome segregation

2012 ◽  
Vol 125 (4) ◽  
pp. 906-918 ◽  
Author(s):  
Nunu Mchedlishvili ◽  
Samuel Wieser ◽  
René Holtackers ◽  
Julien Mouysset ◽  
Mukta Belwal ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Centrosome Separation

scholarly journals Prophase-Specific Perinuclear Actin Coordinates Centrosome Separation and Positioning to Ensure Accurate Chromosome Segregation

Cell Reports ◽  
2020 ◽  
Vol 31 (8) ◽  
pp. 107681 ◽  
Author(s):  
Tom Stiff ◽  
Fabio R. Echegaray-Iturra ◽  
Harry J. Pink ◽  
Alex Herbert ◽  
Constantino Carlos Reyes-Aldasoro ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Centrosome Separation

scholarly journals The Drosophila Kinesin-like Protein KLP67A Is Essential for Mitotic and Male Meiotic Spindle Assembly

2004 ◽  
Vol 15 (1) ◽  
pp. 121-131 ◽  
Author(s):  
Rita Gandhi ◽  
Silvia Bonaccorsi ◽  
Diana Wentworth ◽  
Stephen Doxsey ◽  
Maurizio Gatti ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Mutational Analysis ◽  
Spindle Assembly ◽  
Male Meiosis ◽  
Meiotic Spindle ◽  
Drosophila Cell ◽  
Centrosome Separation ◽  
Mutant Cells

We have performed a mutational analysis together with RNA interference to determine the role of the kinesin-like protein KLP67A in Drosophila cell division. During both mitosis and male meiosis, Klp67A mutations cause an increase in MT length and disrupt discrete aspects of spindle assembly, as well as cytokinesis. Mutant cells exhibit greatly enlarged metaphase spindle as a result of excessive MT polymerization. The analysis of both living and fixed cells also shows perturbations in centrosome separation, chromosome segregation, and central spindle assembly. These data demonstrate that the MT plus end-directed motor KLP67A is essential for spindle assembly during mitosis and male meiosis and suggest that the regulation of MT plus-end polymerization is a key determinant of spindle architecture throughout cell division.

scholarly journals The half-bridge component Kar1 promotes centrosome separation and duplication during budding yeast meiosis

2018 ◽  
Vol 29 (15) ◽  
pp. 1798-1810
Author(s):  
Meenakshi Agarwal ◽  
Hui Jin ◽  
Melainia McClain ◽  
Jinbo Fan ◽  
Bailey A. Koch ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Budding Yeast ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Pole Body ◽  
Centrosome Separation ◽  
Chromatid Segregation ◽  
Yeast Meiosis ◽  
Unique Mechanism

The budding yeast centrosome, often called the spindle pole body (SPB), nucleates microtubules for chromosome segregation during cell division. An appendage, called the half bridge, attaches to one side of the SPB and regulates SPB duplication and separation. Like DNA, the SPB is duplicated only once per cell cycle. During meiosis, however, after one round of DNA replication, two rounds of SPB duplication and separation are coupled with homologue segregation in meiosis I and sister-chromatid segregation in meiosis II. How SPB duplication and separation are regulated during meiosis remains to be elucidated, and whether regulation in meiosis differs from that in mitosis is unclear. Here we show that overproduction of the half-bridge component Kar1 leads to premature SPB separation during meiosis. Furthermore, excessive Kar1 induces SPB overduplication to form supernumerary SPBs, leading to chromosome missegregation and erroneous ascospore formation. Kar1-­mediated SPB duplication bypasses the requirement of dephosphorylation of Sfi1, another half-bridge component previously identified as a licensing factor. Our results therefore reveal an unexpected role of Kar1 in licensing meiotic SPB duplication and suggest a unique mechanism of SPB regulation during budding yeast meiosis.

scholarly journals Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis

2015 ◽  
Vol 209 (3) ◽  
pp. 339-348 ◽  
Author(s):  
Suzanna L. Prosser ◽  
Navdeep K. Sahota ◽  
Laurence Pelletier ◽  
Ciaran G. Morrison ◽  
Andrew M. Fry
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Primary Cilia ◽  
Microtubule Nucleation ◽  
Cycle Progression ◽  
Spindle Formation ◽  
Mitotic Entry ◽  
Bipolar Spindle ◽  
Centrosome Separation

Nek5 is a poorly characterized member of the NIMA-related kinase family, other members of which play roles in cell cycle progression and primary cilia function. Here, we show that Nek5, similar to Nek2, localizes to the proximal ends of centrioles. Depletion of Nek5 or overexpression of kinase-inactive Nek5 caused unscheduled separation of centrosomes in interphase, a phenotype also observed upon overexpression of active Nek2. However, separated centrosomes that resulted from Nek5 depletion remained relatively close together, exhibited excess recruitment of the centrosome linker protein rootletin, and had reduced levels of Nek2. In addition, Nek5 depletion led to loss of PCM components, including γ-tubulin, pericentrin, and Cdk5Rap2, with centrosomes exhibiting reduced microtubule nucleation. Upon mitotic entry, Nek5-depleted cells inappropriately retained centrosome linker components and exhibited delayed centrosome separation and defective chromosome segregation. Hence, Nek5 is required for the loss of centrosome linker proteins and enhanced microtubule nucleation that lead to timely centrosome separation and bipolar spindle formation in mitosis.

A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos

Development ◽  
1998 ◽  
Vol 125 (22) ◽  
pp. 4391-4402 ◽  
Author(s):  
J.M. Schumacher ◽  
N. Ashcroft ◽  
P.J. Donovan ◽  
A. Golden
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Centrosomal Protein ◽  
C Elegans ◽  
Developmental Factors ◽  
Centrosome Separation ◽  
Spindle Dynamics ◽  
Bipolar Spindles

S. cerevisiae Ipl1, Drosophila Aurora, and the mammalian centrosomal protein IAK-1 define a new subfamily of serine/threonine kinases that regulate chromosome segregation and mitotic spindle dynamics. Mutations in ipl1 and aurora result in the generation of severely aneuploid cells and, in the case of aurora, monopolar spindles arising from a failure in centrosome separation. Here we show that a related, essential protein from C. elegans, AIR-1 (Aurora/Ipl1 related), is localized to mitotic centrosomes. Disruption of AIR-1 protein expression in C. elegans embryos results in severe aneuploidy and embryonic lethality. Unlike aurora mutants, this aneuploidy does not arise from a failure in centrosome separation. Bipolar spindles are formed in the absence of AIR-1, but they appear to be disorganized and are nucleated by abnormal-looking centrosomes. In addition to its requirement during mitosis, AIR-1 may regulate microtubule-based developmental processes as well. Our data suggests AIR-1 plays a role in P-granule segregation and the association of the germline factor PIE-1 with centrosomes.

scholarly journals Timing of centrosome separation is important for accurate chromosome segregation

2012 ◽  
Vol 23 (3) ◽  
pp. 401-411 ◽  
Author(s):  
William T. Silkworth ◽  
Isaac K. Nardi ◽  
Raja Paul ◽  
Alex Mogilner ◽  
Daniela Cimini
Keyword(s):  
Nuclear Envelope ◽  
Chromosome Segregation ◽  
Intermediate Stage ◽  
Spindle Pole ◽  
Cellular Space ◽  
Nuclear Envelope Breakdown ◽  
Spindle Poles ◽  
Centrosome Separation ◽  
Large Numbers ◽  
Close Proximity

Spindle assembly, establishment of kinetochore attachment, and sister chromatid separation must occur during mitosis in a highly coordinated fashion to ensure accurate chromosome segregation. In most vertebrate cells, the nuclear envelope must break down to allow interaction between microtubules of the mitotic spindle and the kinetochores. It was previously shown that nuclear envelope breakdown (NEB) is not coordinated with centrosome separation and that centrosome separation can be either complete at the time of NEB or can be completed after NEB. In this study, we investigated whether the timing of centrosome separation affects subsequent mitotic events such as establishment of kinetochore attachment or chromosome segregation. We used a combination of experimental and computational approaches to investigate kinetochore attachment and chromosome segregation in cells with complete versus incomplete spindle pole separation at NEB. We found that cells with incomplete spindle pole separation exhibit higher rates of kinetochore misattachments and chromosome missegregation than cells that complete centrosome separation before NEB. Moreover, our mathematical model showed that two spindle poles in close proximity do not “search” the entire cellular space, leading to formation of large numbers of syntelic attachments, which can be an intermediate stage in the formation of merotelic kinetochores.

Aurora/Ipl1p-related kinases, a new oncogenic family of mitotic serine-threonine kinases

1999 ◽  
Vol 112 (21) ◽  
pp. 3591-3601 ◽  
Author(s):  
R. Giet ◽  
C. Prigent
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drosophila Melanogaster ◽  
Chromosome Segregation ◽  
Mammalian Cells ◽  
Spindle Assembly ◽  
Mitotic Apparatus ◽  
Bipolar Spindle ◽  
The Past ◽  
Centrosome Separation ◽  
Threonine Kinases

During the past five years, a growing number of serine-threonine kinases highly homologous to the Saccharomyces cerevisiae Ipl1p kinase have been isolated in various organisms. A Drosophila melanogaster homologue, aurora, was the first to be isolated from a multicellular organism. Since then, several related kinases have been found in mammalian cells. They localise to the mitotic apparatus: in the centrosome, at the poles of the bipolar spindle or in the midbody. The kinases are necessary for completion of mitotic events such as centrosome separation, bipolar spindle assembly and chromosome segregation. Extensive research is now focusing on these proteins because the three human homologues are overexpressed in various primary cancers. Furthermore, overexpression of one of these kinases transforms cells. Because of the myriad of kinases identified, we suggest a generic name: Aurora/Ipl1p-related kinase (AIRK). We denote AIRKs with a species prefix and a number, e.g. HsAIRK1.

Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation

2002 ◽  
Vol 4 (4) ◽  
pp. 318-322 ◽  
Author(s):  
Niels Mailand ◽  
Claudia Lukas ◽  
Brett K. Kaiser ◽  
Peter K. Jackson ◽  
Jiri Bartek ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Centrosome Separation

scholarly journals Impaired chromosome segregation results in sperms with excess centrosomes in emb-27APC6 mutant C. elegans

2018 ◽  
Author(s):  
Tomo Kondo ◽  
Akatsuki Kimura
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Anaphase Promoting Complex ◽  
C Elegans ◽  
Secondary Spermatocyte ◽  
Centrosome Separation ◽  
A Subunit ◽  
Excess Number

AbstractThe anaphase-promoting complex (APC) is a major regulator of chromosome segregation and is implicated in centriole engagement, whose de-regulation causes abnormal number of centrosomes. The emb-27 gene in C. elegans encodes a subunit of APC. The paternal emb-27 mutant was reported to show cell division with multiple furrows, suggesting the presence of excess centrosomes. In this study, we examined the number of centrosomes and the mechanism underlying de-regulation of centrosome number in emb-27 mutants. Our observations indicated excess centrosomes in emb-27 sperms, which resulted in zygotes with excess centrosomes. Further, the secondary spermatocyte of emb-27 produced reduced number of spermatids, which is likely the direct cause of the excess number of centrosomes per sperm. We propose that a chromosome segregation defect in emb-27 induced centrosome separation defect, resulting in reduced number of buds. Additionally, treatment with cytoskeletal inhibiting drugs indicated presence of three kinds of forces working in combination to move the centrosomes into the spermatids. The present study suggested a novel role of microtubule in the budding cytokinesis of spermatocytes.

Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space

2020 ◽  
Vol 64 (2) ◽  
pp. 251-261
Author(s):  
Jessica E. Fellmeth ◽  
Kim S. McKim
Keyword(s):  
Chromosome Segregation ◽  
New Technologies ◽  
Early Prophase ◽  
Unique Role ◽  
Kinetochore Assembly ◽  
M Phase ◽  
In Vivo Analysis ◽  
Meiosis I

Abstract While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Centromere establishment and stability require CENP-C loading at the centromere for CENP-A function. Pre-meiotic loading of proteins necessary for homolog recombination as well as cohesion also rely on CENP-C, as do the main scaffolding components of the kinetochore. Much of this work relies on new technologies that enable in vivo analysis of meiosis like never before. Here, we strive to highlight the unique role of this highly conserved centromere protein that loads on to centromeres prior to M-phase onset, but continues to perform critical functions through chromosome segregation. CENP-C is not merely a structural link between the centromere and the kinetochore, but also a functional one joining the processes of early prophase homolog synapsis to late metaphase kinetochore assembly and signaling.

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