Mitosis

Nicklas, R. Bruce

doi:10.1007/978-1-4615-9588-5_5

Cited by 204 publications

(62 citation statements)

References 242 publications

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“…Syntelic orientation could result from the collapse of a bipolar spindle, but our observations suggest that Hec1 S165A -expressing cells entering mitosis gain this syntelic orientation by de novo capture of microtubules by both kinetochores in a sister pair. Syntelic orientation is a common error early in meiotic spindles (Nicklas 1971), but its prevalence in early mitosis is less clear. A systematic analysis of the frequency at which syntelic orientation of chromosomes occurs by spontaneous mistakes during mitosis has not been documented.…”

Section: Discussionmentioning

confidence: 99%

The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability

Cai

Yao

et al. 2008

Oncogene

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Loss or gain of whole chromosome, the form of chromosome instability commonly associated with cancers is thought to arise from aberrant chromosome segregation during cell division. Chromosome segregation in mitosis is orchestrated by the interaction of kinetochores with spindle microtubules. Our studies show that NEK2A is a kinetochore-associated protein kinase essential for faithful chromosome segregation. However, it was unclear how NEK2A ensures accurate chromosome segregation in mitosis. Here we show that NEK2A-mediated Hec1 (highly expressed in cancer) phosphorylation is essential for faithful kinetochore microtubule attachments in mitosis. Using phospho-specific antibody, our studies show that NEK2A phosphorylates Hec1 at Ser165 during mitosis. Although such phosphorylation is not required for assembly of Hec1 to the kinetochore, expression of non-phosphorylatable mutant Hec1 S165 perturbed chromosome congression and resulted in a dramatic increase in microtubule attachment errors, including syntelic and monotelic attachments. Our in vitro reconstitution experiment demonstrated that Hec1 binds to microtubule in low affinity and phosphorylation by NEK2A, which prevents aberrant kinetochore-microtubule connections in vivo, increases the affinity of the Ndc80 complex for microtubules in vitro. Thus, our studies illustrate a novel regulatory mechanism in which NEK2A kinase operates a faithful chromosome attachment to spindle microtubule, which prevents chromosome instability during cell division.

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Section: Discussionmentioning

confidence: 99%

The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability

Cai

Yao

et al. 2008

Oncogene

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“…The question of why chromosomes of vastly different sizes within the same cell move at the same rate in anaphase has puzzled investigators for many years (see reviews of Nicklas [27] and Bajer and Mol6-Bajer [3]) . There is a range of anaphase velocities among different species from 0.2 ,um/min to 8 Am/min (20), but it is not yet clear whether this range is correlated with chromosome size .…”

Section: Discussionmentioning

confidence: 99%

Chromosome behavior after laser microirradiation of a single kinetochore in mitotic PtK2 cells.

McNeill¹,

Berns²

1981

The Journal of Cell Biology

130

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The role of the kinetochore in chromosome movement was studied by 532-nm wavelength laser microirradiation of mitotic PtK2 cells. When the kinetochore of a single chromatid is irradiated at mitotic prometaphase or metaphase, the whole chromosome moves towards the pole to which the unirradiated kinetochore is oriented, while the remaining chromosomes congregate on the metaphase plate. The chromatids of the irradiated chromosome remain attached to one another until anaphase, at which time they separate by a distance of 1 or 2 p,m and remain parallel to each other, not undergoing any poleward separation . Electron microscopy shows that irradiated chromatids exhibit either no recognizable kinetochore structure or a typical inactive kinetochore in which the tri-layer structure is present but has no microtubules associated with it . Graphical analysis of the movement of the irradiated chromosome shows that the chromosome moves to the pole rapidly with a velocity of -3 ,um/ min . If the chromosome is close to one pole at irradiation, and the kinetochore oriented towards that pole is irradiated, the chromosome moves across the spindle to the opposite pole . The chromosome is slowed down as it traverses the equatorial region, but the velocity in both half-spindles is approximately the same as the anaphase velocity of a single chromatid . Thus a single kinetochore moves twice the normal mass of chromatin (two chromatids) at the same velocity with which it moves a single chromatid, showing that the velocity with which a kinetochore moves is independent, within limits, of the mass associated with it .It is now generally accepted that mitotic spindle formation and chromosome movement involve several structures, including microtubules, centrioles, pericentriolar regions, and the centromere regions of the chromosomes . There have been several investigations into the ultrastructure and chemical composition of the kinetochore, or attachment site of microtubules to the centromeric region (14,(30)(31)(32)35) . Electron microscope studies have revealed a relatively uniform morphology of the kinetochore region in many different eukaryotes (including PtK 2 cells [34]) consisting of a trilaminar structure 0 .3-0 .6 ttm in diameter.Although the kinetochore has been demonstrated unequivocally to be a microtubule-organizing center in vitro (15,22,36,38), very little biochemical information is available on it . However, there are indications that ribonucleoprotein is a component of the kinetochore (9, 32) and it appears to be associated with the inner plate of the trilaminar kinetochore in PtK, cells .One of the earliest studies on the function of the centromere pertains to the mitotic behavior of x-ray-induced chromosome fragments lacking centromeres (11,12). Although these fragments did not join the metaphase plate, there was some sepa-THE JOURNAL OF CELL BIOLOGY " VOLUME 88 MARCH 1981 543-553 ©The Rockefeller University Press " 0021-9525/81/03/0543/11 $1 .00 ration of the chromatids at anaphase. However, they lagged behind the...

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“…Whether the geometry mechanism is sufficient to ensure bi-orientation in mitosis has been a source of argument (Nicklas 1971;Ault & Rieder 1992). If this were the case, and if mal-orientation were never corrected after this happened inadvertently, the frequencyof mal-orientation should be very lowthroughout mitosis (otherwise cells cannot maintain their ploidy with high fidelity).…”

Section: Mal-orientation: Avoided or Corrected?mentioning

confidence: 99%

Chromosome bi-orientation on the mitotic spindle

Tanaka

2005

Phil. Trans. R. Soc. B

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For proper chromosome segregation, sister kinetochores must attach to microtubules extending from opposite spindle poles prior to anaphase onset. This state is called sister kinetochore bi-orientation or chromosome bi-orientation. The mechanism ensuring chromosome bi-orientation lies at the heart of chromosome segregation, but is still poorly understood. Recent evidence suggests that mal-oriented kinetochore-to-pole connections are corrected in a tension-dependent mechanism. The cohesin complex and the Ipl1/Aurora B protein kinase seem to be key regulators for this correction. In this article, I discuss how cells ensure sister kinetochore bi-orientation for all chromosomes, mainly focusing on our recent findings in budding yeast.

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Mitosis

Cited by 204 publications

References 242 publications

The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability

The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability

Chromosome behavior after laser microirradiation of a single kinetochore in mitotic PtK2 cells.

Chromosome bi-orientation on the mitotic spindle

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