Kinetochore Assembly
Kinetochore assembly - The key site for attachment of the chromosome to the mitotic spindle is the kinetochore. Kinetochores demonstrate amazing variability in eukaryotes: budding yeast employ a minimalist kinetochore that appears to bind only a single microtubule, human kinetochores are complex multiprotein structures that bind many microtubules, and nematode worms expand their kinetochores so that they occupy the entire length of the chromosome. We are attempting to understand the underlying principles that give rise to this diversity of kinetochore structures but still allow the common function of microtubule binding during mitosis.
We are particularly interested in how the chromatin of the centromere is distinguished so that kinetochores are assembled only at this site of specialized chromatin. Centromeric chromatin is uniquely identified by the replacement of histone H3 in the nucleosome with the histone H3 variant centromere protein A (CENP-A). We are studying how these specialized nucleosomes are deposited in centromeric chromatin, how this chromatin is stably propagated through many cell divisions, and how CENP-A templates the assembly of the higher-order kinetochore structure.
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