Histones centromeric chromatin

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. 

The ultimate job of the SAC is to ensure that cells enter anaphase only after all chromosomes have acquired a bipolar (i.e., amphitelic) attachment to the spindle. As described earlier, the checkpoint signal is initiated at kinetochores that either are not attached to the spindle or display a loss of tension. The kineto-chore is composed of many specific proteins that play two crucial roles (1) coordinate attachment to microtubules, and (2) send signals when attachments are incorrect. Kinetochores are assembled by a complicated process at the centromere, a specific region of the chromosome characterized by the presence of nucleotide repeats. Thus, it is the DNA sequence that ultimately determines where the kinetochore will assemble. Centromeric chromatin is also characterized by the presence of a variant histone, CENP-A, which takes the place of histone H3 in the nucleosome core. 

Additional substrates of Aurora B include CENP-A, a histone H3 variant found only in centromeric chromatin. This phosphorylation has been implicated in the translocation of the CPC to the spindle midzone. INCENP is also phosphorylated by Aurora B, which enhances the ability of INCENP to activate Aurora B. As described earlier, one of the important functions of Aurora B kinase is in the destabilization of inappropriate spindle-kinetochore attachments. Aurora B is also required for the SAC, however its targets in this checkpoint are not knovm. 

The recent reconstitution of CENP-A containing nucleosomes confirms the ability of these histones to form nucleosome assemblies in specialized chromatin domains [66] although the stability and structure of these nucleosome particles remain to be defined. At first glance, the dynamic nature of centromeres during chromosome motility suggests that CENP-A may contribute to enhance the... 

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