Centromere Kinetochore structure

Centromer-specific H3 variants (CenH3 s) are known as CENP-A in mammals, Cid in flies, Cse4 in yeast (Fig. 1 Table 1 reviewed in Smith 2002). CenH3 s are incorporated into nucleosomes independently of centromeric DNA replication. CenH3-containing nucleosomes associate with a number of factors with important roles in centromere structure and kinetochore assembly. Recently, the deposition complex... 

The lower evolutionary constraint on the sequences of CENP-A-type variants in comparison to most other core histone variants could in part reflect the very limited context in which CENP-A functions, i.e., only in centromeric chromatin associated with the kinetochore. Most other variants appear to be rather widely distributed in the chromatin, and therefore, may be involved in a greater variety of interactions and modifications that could constrain their structure during evolution. 

Warburton, P.E., Cooke, C.A., Bourassa, S., Vafa, O., Sullivan, B.A., Stetten, G., Gimelli, G., Warburton, D., Tyler-Smith, C., Sullivan, K.F., Poirier, G.G., and Earnshaw, W.C. (1997) Immunolocalization of CENP-A suggests a distinct nucleosome structure at the inner kinetochore plate of active centromeres. Current Biol. 7, 901-904. 

Kinetochore. A structure that attaches laterally to the centromere of a chromosome it is the site of chromosome tubule attachment. 

Three types of microtubule can readily be defined in the mitotic spindle. Polar microtubules overlap (and probably interact) between the poles and are involved in pushing the poles apart in anaphase. Astral microtubules radiate in all directions and also help separate the poles. Kinetochore microtubules attach themselves to specialized protein structures (kinetochores) located on each side of the centromere of each chromosome. These microtubules are involved in moving the chromosomes to the metaphase plate and in separating sister chromatids at anaphase. The microtubules in the spindle are very dynamic and have a half-life of only a few seconds. This appears to be especially important in the capture of chromosomes by the kinetochore microtubules. Microtubules that miss the target kinetochores are quickly lost because their dynamic instability soon leads to depolymerization. The new microtubules that form may hit the target and be partially stabilized through plus-end capping. 

In higher eukaryotes, a complex protein structure called the kinetochore assembles at centromeres and associates with multiple mitotic spindle fibers during mitosis. Homologs of most of the centromeric proteins found in the yeasts occur in humans and other higher eukaryotes and are thought to be components of kinetochores. The role of the centromere and proteins that bind to it in the segregation of sister chromatids during mitosis is described in Chapters 20 and 21. 

CENP-A to CENP-G) bind to the DNA sequences of centromeres and direct the formation of fhe kinetochores. Even for the simpler centromere of budding yeasfs, kinetochores have a complex structure.The CENT proteins were first idenhfied as autoantigens in sera of patients with the autoimmune disorder scleroderma (Chapter... 

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