Chromosome metaphase

The phase of the cell cycle where the sister chromatids are separated and distributed onto two daughter nuclei. First, upon entry into mitosis the chromosomes are condensed followed by the breakdown of the nuclear-envelope (prophase). The two centrosomes are separated and induce the formation of the mitotic spindle. Then, the chromosomes are captures by the spindle and aligned on the metaphase plate (metaphase). The sister-chromatids are separated and pulled to the poles of the spindle (anaphase). In telophase, two new nuclei are formed around the separated chromatids. 

A signal transduction pathway required for proper chromosome alignment during mitosis. The spindle assembly checkpoint is activated during mitosis in response to the presence of chromosomes that are not attached to spindle microtubules or that are not properly aligned at the metaphase plate. The spindle checkpoint... 

Several groups of drugs that bind to tubulin at different sites interfere with its polymerization into microtubules. These drugs are of experimental and clinical importance (Bershadsky and Vasiliev, 1988). For example, colchicine, an alkaloid derived from the meadow saffron plant Colchicum autumnale or Colchicum speciosum), is the oldest and most widely studied of these drugs. It forms a molecular complex with tubulin in the cytosol pool and prevents its polymerization into microtubules. Other substances such as colcemid, podophyllotoxin, and noco-dazole bind to the tubulin molecule at the same site as colchicine and produce a similar effect, albeit with some kinetic differences. Mature ciliary microtubules are resistant to colchicine, whereas those of the mitotic spindle are very sensitive. Colchicine and colcemid block cell division in metaphase and are widely used in cytogenetic studies of cultured cells to enhance the yield of metaphase plate chromosomes. 

Figure 36-3. Shown is the extent of DNA packaging in metaphase chromosomes (fop) to noted dupiex DNA (bottom). Chromosomai DNA is packaged and organized at severai ieveis as shown (seeTabie 36-2), Each phase of condensation or compaction and organization (bottom to top) decreases overaii DNA accessibiiity to an extent that the DNA sequences in metaphase chromosomes are aimost totaiiy transcriptionaiiy inert, in toto, these five ieveis of DNA compaction resuit in neariy a 10 -foid iinear decrease in end-to-end DNA iength. Compiete condensation and decondensation of the iinear DNA in chromosomes occur in the space of hours during the normai repiicative ceii cycie (see Figure 36-20).

At metaphase, mammalian chromosomes possess a twofold symmetry, with the identical duplicated sister chromatids connected at a centromere, the relative po-... 

Figure 36-6. A human karyotype (of a man with a normal 46,XY constitution), in which the metaphase chromosomes have been stained by the Giemsa method and aligned according to the Paris Convention. (Courtesy of H Lawce and F Conte.)...

Figure 36-9. The process of crossing-over between homologous metaphase chromosomes to generate recombinant chromosomes. See also Figure 36-12.

Lewis, C.D. and Laemmli, U.K. (1982). Higher order metaphase chromosome structure evidence for metal-loprotein interactions. Cell 29, 171-181. 

The duration of the M phase is largely determined by the time necessary for the formation of a functional metaphase spindle and the correct alignment of all chromosomes in the metaphase plate. The spindle assembly checkpoint prevents the exit from the M phase before the proper alignment of all chromosomes into a metaphase plate in many cell types. This kind of control is already operational... 

FIG. 3. Chromosome arms begin to separate in pro metaphase. Scanning electron micrographs of human chromosomes isolated from cells in prophase (A), prometaphase (B), metaphase (C) and early anaphase (insert in C). Size bar, 1 /tm. Reprinted with permission from Sumner (1991). 

The non-cleavage pathway would remove most cohesin during prophase/ pro-metaphase by an as yet obscure mechanism. This pathway could involve phosphorylation of a cohesin subunit by mitotic protein kinases, because vertebrate cohesins rebind to chromatin in telophase when mitotic kinases are inactivated and chromosomes decondense (Losada et al 1998). The dissociation of cohesin from chromatin during prophase coincides with, but does not depend on, the association of condensin with chromosomes. This first phase of cohesin removal may be crucial (possibly along with the arrival of... 

The pall of fog that has shrouded the sister separation process for over a century is starting to lift and this long mysterious process has started to reveal its secrets. There is now convincing evidence that the sudden movement of chromosomes to the poles at the onset of anaphase is triggered by cleavage of specific sister chromatid cohesion proteins. Future research must address the structural basis of cohesion and how it is established only at replication forks. It must also address the generality of mechanisms that dismantle cohesion at the metaphase to anaphase transition and how mistakes in this process contribute to human disease. 

Khodjakov A, ColeRW, Bajer AS,Rieder CL 1996 The force for poleward chromosome motion in Haemanthus cells acts along the length of the chromosome during metaphase but only at the kinetochore during anaphase. J Cell Biol 132 1093—1104... 

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