?Dumb? versus ?smart? kinetochore models for chromosome congression during mitosis in vertebrate somatic cells
✍ Scribed by Khodjakov, Alexey ;Gabashvili, Irene S. ;Rieder, Conly L.
- Book ID
- 101230629
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 130 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0886-1544
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✦ Synopsis
During mitosis, a replicated chromosome establishes a bipolar attachment to the forming spindle as its two sister kinetochores acquire chromosomal or kinetochore fibers (K-fibers). These K-fibers consist of microtubule (Mt) bundles that function not only to tether the chromosome to the spindle poles, but they also serve as a scaffold against which the forces for chromosome poleward (P) motion are generated.
In vertebrates, K-fibers are formed as a kinetochore encounters dynamically unstable Mts growing from one of the spindle poles (centrosomes). Because of the random nature of this attachment mechanism, K-fibers rarely form simultaneously on sister kinetochores. Instead, the kinetochore closest to and facing a pole at the time of nuclear envelope breakdown is usually the first to attach, and as it does so, it moves the chromosome rapidly into the pole it is attaching to [e.g., Rieder and Alexander, 1990]. The now ''monooriented'' chromosome then remains firmly associated with this pole until its unattached kinetochore, located on the opposite side of its primary constriction, becomes attached to a Mt growing from the distal pole [McEwen et al., 1997]. For any one chromosome, the monoorientation stage may be brief, as when K-fibers form rapidly on both sister kinetochores, or it may last for several hours if the chromosome is trapped behind a pole [see Rieder et al., 1994]. Regardless, when a Mt growing from the distal pole finally contacts the unattached kinetochore, the now ''bioriented'' chromosome undergoes a series of motions that result in its displacement away from the proximal and towards the distal pole. These motions constitute the process of congression [Darlington, 1937], which ultimately positions the bioriented chromosome on the spindle equator midway between the two poles.
''SMART KINETOCHORE'' MODELS FOR CONGRESSION
The mechanism(s) underlying congression have perplexed students of mitosis since the process was first described in the 1880s. One of the earliest models envisioned that the alignment of a chromosome on the spindle equator was due simply to repulsive forces generated by both of the poles [Darlington, 1937]. Although never disproved (see below), this hypothesis was subsequently abandoned in lieu of the more testable idea that chromosomes are pulled to the spindle equator by the action of their associated the K-fibers. In its best developed form, this hypothesis envisions that congression occurs because the P force acting on each sister kinetochore is always on, that this P force is produced along the length of the K-fiber, and that its magnitude is proportional to K-fiber length [e.g.,