Centromere and Kinetochore Assembly
Centromere and Kinetochore assembly - The key site for attachment of the chromosome to the mitotic spindle is the kinetochore. Kinetochores demonstrate amazing structural diversity: budding yeast employ a minimalist kinetochore that binds a single microtubule, human kinetochores bind approximately 20 microtubules, and nematode worms expand their kinetochores so that they occupy the entire length of the chromosome. Despite organizational differences, many of the core proteins of the kinetochore are conserved throughout eukaryotes. 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.
The kinetochore is a transient structure that only exists during mitosis and is disassembled after cells segregate their chromosomes and rebuild the nuclear envelope. However, the underlying foundation for the kinetochore, the centromere, persists throughout the cell cycle. The centromere is comprised of a uniquely specialized region of chromatin and a core complex of approximately 20 constitutively associated proteins. Centromeric chromatin is distinguished by the replacement of histone H3 in the nucleosome with the histone H3 variant centromere protein A (CENP-A) that is thought to epigenetically specify centromere function. We are particularly interested in how centromeric chromatin is assembled and how that chromatin directs the assembly of the centromere and the mitotic kinetochore. We are studying how the specialized centromeric nucleosomes are deposited in centromeric chromatin, how this chromatin is stably propagated through many cell divisions, and how CENP-A chromatin is recognized to build the centromere and mitotic kinetochore.