Centromeric variants

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... 

Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H (2002) Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35 243-254 Smith MM (2002) Centromeres and variant histones what, where, when and why Curr Opin Cell Biol 14 279-285... 

Centromere protein A (CENP-A), one of several variants of histone H3, is phosphorylated on Ser 7 by Aurora B kinase which is equivalent to Ser 10 of histone H3 (Zeitlin et al, 2001). Recent studies demonstrate that Aurora A kinase also phosphorylates CENP-A (S7) (Kunitoku et al, 2003) (Table 1). The presence of CENP-A in centromeric nucleosomes is required for kinetochore organization and function (Choo 2001). Loss of CENP-A phosphorylation function at Ser 7 caused a mislocalisation of Aurora B, a putative partner phosphatase (PPl-yl) and inner centromere protein (INCENP). H3.3, another variant of histone H3 is phosphorylated on Ser 31 in vivo (Table 1). H3.3 (S31) is a mitosis-specific modification that is present only in late prometaphase and metaphase. Furthermore, H3.3 (S31) is excluded from centromeres. However it is enriched in distinct chromosomal areas immediately adjacent to centromeres (Hake et al, 2005). 

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 centromeric-specific histone H3-like variant, CENP-A, that is present in all eukaryotes is phosphorylated by aurora B at Ser-7 and dephosphosphorylated by... 

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. 

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