Faculty Opinions recommendation of The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment.

2008 ◽  
Author(s):  
Duane Compton
Keyword(s):  
Mitotic Chromosome ◽  
Chromosome Alignment

scholarly journals KIF18A's neck linker permits navigation of microtubule-bound obstacles within the mitotic spindle

2019 ◽  
Vol 2 (1) ◽  
pp. e201800169 ◽  
Author(s):  
Heidi LH Malaby ◽  
Dominique V Lessard ◽  
Christopher L Berger ◽  
Jason Stumpff
Keyword(s):  
Single Molecule ◽  
Mitotic Spindle ◽  
Binding Proteins ◽  
Mitotic Chromosome ◽  
Chromosome Movement ◽  
Wild Type ◽  
Microtubule Associated Proteins ◽  
Chromosome Alignment ◽  
Associated Proteins ◽  
Fiber Dynamics

KIF18A (kinesin-8) is required for mammalian mitotic chromosome alignment. KIF18A confines chromosome movement to the mitotic spindle equator by accumulating at the plus-ends of kinetochore microtubule bundles (K-fibers), where it functions to suppress K-fiber dynamics. It is not understood how the motor accumulates at K-fiber plus-ends, a difficult feat requiring the motor to navigate protein dense microtubule tracks. Our data indicate that KIF18A's relatively long neck linker is required for the motor's accumulation at K-fiber plus-ends. Shorter neck linker (sNL) variants of KIF18A display a deficiency in accumulation at the ends of K-fibers at the center of the spindle. Depletion of K-fiber–binding proteins reduces the KIF18A sNL localization defect, whereas their overexpression reduces wild-type KIF18A's ability to accumulate on this same K-fiber subset. Furthermore, single-molecule assays indicate that KIF18A sNL motors are less proficient in navigating microtubules coated with microtubule-associated proteins. Taken together, these results support a model in which KIF18A's neck linker length permits efficient navigation of obstacles to reach K-fiber ends during mitosis.

scholarly journals B56-PP2A regulates motor dynamics for mitotic chromosome alignment

2014 ◽  
Vol 127 (21) ◽  
pp. 4567-4573 ◽  
Author(s):  
P. Xu ◽  
D. M. Virshup ◽  
S. H. Lee
Keyword(s):  
Mitotic Chromosome ◽  
Chromosome Alignment ◽  
Motor Dynamics

scholarly journals Contribution of hCAP-D2, a Non-SMC Subunit of Condensin I, to Chromosome and Chromosomal Protein Dynamics during Mitosis

2005 ◽  
Vol 25 (2) ◽  
pp. 740-750 ◽  
Author(s):  
Erwan Watrin ◽  
Vincent Legagneux
Keyword(s):  
Rna Interference ◽  
Mitotic Spindle ◽  
Topoisomerase Ii ◽  
Mitotic Chromosome ◽  
Chromosomal Protein ◽  
Structural Components ◽  
Mitotic Chromosomes ◽  
Sister Chromatids ◽  
Chromosome Alignment ◽  
Structural Maintenance Of Chromosomes

ABSTRACT Condensins are heteropentameric complexes that were first identified as structural components of mitotic chromosomes. They are composed of two SMC (structural maintenance of chromosomes) and three non-SMC subunits. Condensins play a role in the resolution and segregation of sister chromatids during mitosis, as well as in some aspects of mitotic chromosome assembly. Two distinct condensin complexes, condensin I and condensin II, which differ only in their non-SMC subunits, exist. Here, we used an RNA interference approach to deplete hCAP-D2, a non-SMC subunit of condensin I, in HeLa cells. We found that the association of hCAP-H, another non-SMC subunit of condensin I, with mitotic chromosomes depends on the presence of hCAP-D2. Moreover, chromatid axes, as defined by topoisomerase II and hCAP-E localization, are disorganized in the absence of hCAP-D2, and the resolution and segregation of sister chromatids are impaired. In addition, hCAP-D2 depletion affects chromosome alignment in metaphase and delays entry into anaphase. This suggests that condensin I is involved in the correct attachment between chromosome kinetochores and microtubules of the mitotic spindle. These results are discussed relative to the effects of depleting both condensin complexes.

scholarly journals The kinesin-14 Klp2 is negatively regulated by the SIN for proper spindle elongation and telophase nuclear positioning

2012 ◽  
Vol 23 (23) ◽  
pp. 4592-4600 ◽  
Author(s):  
Sebastian Mana-Capelli ◽  
Janel R. McLean ◽  
Chun-Ti Chen ◽  
Kathleen L. Gould ◽  
Dannel McCollum
Keyword(s):  
Mitotic Chromosome ◽  
Microtubule Organizing Center ◽  
Nuclear Positioning ◽  
Mitotic Kinase ◽  
Division Site ◽  
Chromosome Alignment ◽  
Organizing Center ◽  
Septation Initiation Network ◽  
Spindle Elongation ◽  
Kinase Pathway

In Schizosaccharomyces pombe, a late mitotic kinase pathway called the septation initiation network (SIN) triggers cytokinesis. Here we show that the SIN is also involved in regulating anaphase spindle elongation and telophase nuclear positioning via inhibition of Klp2, a minus end–directed kinesin-14. Klp2 is known to localize to microtubules (MTs) and have roles in interphase nuclear positioning, mitotic chromosome alignment, and nuclear migration during karyogamy (nuclear fusion during mating). We observe SIN-dependent disappearance of Klp2 from MTs in anaphase, and we find that this is mediated by direct phosphorylation of Klp2 by the SIN kinase Sid2, which abrogates loading of Klp2 onto MTs by inhibiting its interaction with Mal3 (EB1 homologue). Disruption of Klp2 MT localization is required for efficient anaphase spindle elongation. Furthermore, when cytokinesis is delayed, SIN inhibition of Klp2 acts in concert with microtubules emanating from the equatorial microtubule-organizing center to position the nuclei away from the cell division site. These results reveal novel functions of the SIN in regulating the MT cytoskeleton and suggest that the SIN may have broader functions in regulating cellular organization in late mitosis than previously realized.

scholarly journals Molecular mechanism underlying the non-essentiality of Bub1 for the fidelity of chromosome segregation in human cells

2021 ◽  
Author(s):  
Qinfu Chen ◽  
Miao Zhang ◽  
Xuan Pan ◽  
Linli Zhou ◽  
Haiyan Yan ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Chromosome ◽  
Threshold Level ◽  
Underlying Mechanism ◽  
Human Cells ◽  
Strong Reduction ◽  
Checkpoint Signaling ◽  
Chromosome Alignment ◽  
Redundant Role

SUMMARYThe multi-task protein kinase Bub1 has long been considered important for chromosome alignment and spindle assembly checkpoint signaling during mitosis. However, recent studies provide surprising evidence that Bub1 may not be essential in human cells, with the underlying mechanism unknown. Here we show that Bub1 plays a redundant role with the non-essential CENP-U complex in recruiting Polo-like kinase 1 (Plk1) to the kinetochore. While disrupting either pathway of Plk1 recruitment does not affect the accuracy of whole chromosome segregation, loss of both pathways leads to a strong reduction in the kinetochore accumulation of Plk1 under a threshold level required for proper chromosome alignment and segregation. Thus, parallel recruitment of Plk1 to kinetochores by Bub1 and the CENP-U complex ensures high fidelity of mitotic chromosome segregation. This study may have implications for targeted treatment of cancer cells harboring mutations in either Bub1 or the CENP-U complex.

scholarly journals A Microtubule-Associated Zinc Finger Protein, BuGZ, Regulates Mitotic Chromosome Alignment by Ensuring Bub3 Stability and Kinetochore Targeting

2014 ◽  
Vol 28 (3) ◽  
pp. 268-281 ◽  
Author(s):  
Hao Jiang ◽  
Xiaonan He ◽  
Shusheng Wang ◽  
Junling Jia ◽  
Yihan Wan ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Mitotic Chromosome ◽  
Zinc Finger Protein ◽  
Finger Protein ◽  
Chromosome Alignment

scholarly journals Cell division requires RNA eviction from condensing chromosomes

2020 ◽  
Vol 219 (11) ◽  
Author(s):  
Judith A. Sharp ◽  
Carlos Perea-Resa ◽  
Wei Wang ◽  
Michael D. Blower
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Aurora B ◽  
Nucleic Acid Binding ◽  
Mitotic Chromosomes ◽  
Nuclear Envelope Breakdown ◽  
Binding Domains ◽  
Chromosome Alignment ◽  
Rna Complexes

During mitosis, the genome is transformed from a decondensed, transcriptionally active state to a highly condensed, transcriptionally inactive state. Mitotic chromosome reorganization is marked by the general attenuation of transcription on chromosome arms, yet how the cell regulates nuclear and chromatin-associated RNAs after chromosome condensation and nuclear envelope breakdown is unknown. SAF-A/hnRNPU is an abundant nuclear protein with RNA-to-DNA tethering activity, coordinated by two spatially distinct nucleic acid–binding domains. Here we show that RNA is evicted from prophase chromosomes through Aurora-B–dependent phosphorylation of the SAF-A DNA-binding domain; failure to execute this pathway leads to accumulation of SAF-A–RNA complexes on mitotic chromosomes, defects in metaphase chromosome alignment, and elevated rates of chromosome missegregation in anaphase. This work reveals a role for Aurora-B in removing chromatin-associated RNAs during prophase and demonstrates that Aurora-B–dependent relocalization of SAF-A during cell division contributes to the fidelity of chromosome segregation.

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