scholarly journals Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly.

1992 ◽  
Vol 118 (1) ◽  
pp. 109-120 ◽  
Author(s):  
M A Hoyt ◽  
L He ◽  
K K Loo ◽  
W S Saunders
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Viability ◽  
Chromosome Segregation ◽  
Heavy Chain ◽  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Gene Products ◽  
Related Gene ◽  
Mitotic Spindle Assembly ◽  
Spindle Microtubules

Two Saccharomyces cerevisiae genes, CIN8 and KIP1 (a.k.a. CIN9), were identified by their requirement for normal chromosome segregation. Both genes encode polypeptides related to the heavy chain of the microtubule-based force-generating enzyme kinesin. Cin8p was found to be required for pole separation during mitotic spindle assembly at 37 degrees C, although overproduced Kip1p could substitute. At lower temperatures, the activity of at least one of these proteins was required for cell viability, indicating that they perform an essential but redundant function. Cin8p was observed to be a component of the mitotic spindle, colocalizing with the microtubules that lie between the poles. Taken together, these findings suggest that these proteins interact with spindle microtubules to produce an outwardly directed force acting upon the poles.

scholarly journals Mitotic Spindle Assembly and Chromosome Segregation

2004 ◽  
Vol 15 (3) ◽  
pp. 317-327 ◽  
Author(s):  
Susan L Kline-Smith ◽  
Claire E Walczak
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Mitotic Spindle Assembly

scholarly journals Microtubule pivoting enables mitotic spindle assembly in S. cerevisiae

2021 ◽  
Vol 220 (3) ◽  
Author(s):  
Kimberly K. Fong ◽  
Trisha N. Davis ◽  
Charles L. Asbury
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Force Generation ◽  
Initial Contact ◽  
Bipolar Spindle ◽  
Spindle Poles ◽  
Mitotic Spindle Assembly ◽  
Spindle Microtubules ◽  
Pole Component

To assemble a bipolar spindle, microtubules emanating from two poles must bundle into an antiparallel midzone, where plus end–directed motors generate outward pushing forces to drive pole separation. Midzone cross-linkers and motors display only modest preferences for antiparallel filaments, and duplicated poles are initially tethered together, an arrangement that instead favors parallel interactions. Pivoting of microtubules around spindle poles might help overcome this geometric bias, but the intrinsic pivoting flexibility of the microtubule–pole interface has not been directly measured, nor has its importance during early spindle assembly been tested. By measuring the pivoting of microtubules around isolated yeast spindle poles, we show that pivoting flexibility can be modified by mutating a microtubule-anchoring pole component, Spc110. By engineering mutants with different flexibilities, we establish the importance of pivoting in vivo for timely pole separation. Our results suggest that passive thermal pivoting can bring microtubules from side-by-side poles into initial contact, but active minus end–directed force generation will be needed to achieve antiparallel alignment.

scholarly journals The nonmotor adaptor HMMR dampens Eg5-mediated forces to preserve the kinetics and integrity of chromosome segregation

2018 ◽  
Vol 29 (7) ◽  
pp. 786-796 ◽  
Author(s):  
Helen Chen ◽  
Marisa Connell ◽  
Lin Mei ◽  
Gregor S. D. Reid ◽  
Christopher A. Maxwell
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Adaptor Proteins ◽  
Microtubule Organization ◽  
Assembly Factor ◽  
Mitotic Spindle Assembly ◽  
Chemical Inhibition ◽  
Kinesin Eg5 ◽  
Interfering Rna

Mitotic spindle assembly and organization require forces generated by motor proteins. The activity of these motors is regulated by nonmotor adaptor proteins. However, there are limited studies reporting the functional importance of adaptors on the balance of motor forces and the promotion of faithful and timely cell division. Here we show that genomic deletion or small interfering RNA silencing of the nonmotor adaptor Hmmr/HMMR disturbs spindle microtubule organization and bipolar chromosome–kinetochore attachments with a consequent elevated occurrence of aneuploidy. Rescue experiments show a conserved motif in HMMR is required to generate interkinetochore tension and promote anaphase entry. This motif bears high homology with the kinesin Kif15 and is known to interact with TPX2, a spindle assembly factor. We find that HMMR is required to dampen kinesin Eg5-mediated forces through localizing TPX2 and promoting the formation of inhibitory TPX2-Eg5 complexes. In HMMR-silenced cells, K-fiber stability is reduced while the frequency of unattached chromosomes and the time needed for chromosome segregation are both increased. These defects can be alleviated in HMMR-silenced cells with chemical inhibition of Eg5 but not through the silencing of Kif15. Together, our findings indicate that HMMR balances Eg5-­mediated forces to preserve the kinetics and integrity of chromosome segregation.

scholarly journals The microtubule-associated protein EML3 regulates mitotic spindle assembly by recruiting the Augmin complex to spindle microtubules

2019 ◽  
Vol 294 (14) ◽  
pp. 5643-5656 ◽  
Author(s):  
Jia Luo ◽  
Biying Yang ◽  
Guangwei Xin ◽  
Mengjie Sun ◽  
Boyan Zhang ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Mitotic Spindle Assembly ◽  
Spindle Microtubules

scholarly journals QN1/KIAA1009: a new essential protein for chromosome segregation and mitotic spindle assembly

Oncogene ◽  
2005 ◽  
Vol 25 (13) ◽  
pp. 1887-1895 ◽  
Author(s):  
A Leon ◽  
B Omri ◽  
A Gely ◽  
C Klein ◽  
P Crisanti
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Essential Protein ◽  
Mitotic Spindle Assembly

scholarly journals Compartimentalized control of Cdk1 drives mitotic spindle assembly

2021 ◽  
Author(s):  
Angela Flavia Serpico ◽  
Francesco Febbraro ◽  
Caterina Pisauro ◽  
Domenico Grieco
Keyword(s):  
Mitotic Spindle ◽  
Kinase Activity ◽  
Spindle Assembly ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
Microtubule Growth ◽  
Mitotic Spindle Assembly ◽  
Spindle Microtubules ◽  
Growth Promoting ◽  
Fraction Bound

During cell division, dramatic microtubular rearrangements driven by cyclin B-cdk1 (Cdk1) kinase activity mark mitosis onset leading to interphase cytoskeleton dissolution and mitotic spindle assembly. Once activated by Cdc25, that reverses inhibitory phosphorylation operated by Wee1/Myt1, Cdk1 clears the cytoplasm from microtubules by inhibiting microtubule associated proteins (MAPs) with microtubule growth-promoting properties. Nevertheless, some of these MAPs are required for spindle assembly, creating quite a conundrum. We show here that a Cdk1 fraction bound to spindle structures escaped Cdc25 action and remained inhibited by phosphorylation (i-Cdk1) in mitotic human cells. Loss or restoration of i-Cdk1 inhibited or promoted spindle assembly, respectively. Furthermore, polymerizing spindle microtubules fostered i-Cdk1 by aggregating with Wee1 and excluding Cdc25. Our data reveal that spindle assembly relies on compartimentalized control of Cdk1 activity.

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