REGULATION OF KINETOCHORE-MICROTUBULE ATTACHMENT BY THE NDC80 COMPLEX

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Faithful mitotic chromosome segregation is essential in the prevention of aneuploid cells, which contain an abnormal number of chromosomes and are present in almost all human solid tumors. Understanding how eukaryotic cells distribute their chromosomes equally is essential in furthering the understanding of cancer cell biology. Chromosomes are segregated via the mitotic spindle, a complex apparatus that consists of a dynamic array of microtubules, and requires the function of numerous proteins at centrosomes, kinetochores, and along spindle microtubules. A critical step in mitosis is attachment of chromosomes to the mitotic spindle. Chromosomes attach to spindle microtubules via their kinetochores, which are large proteinaceous structures located at the primary constriction, or centromere region, of mitotic chromosomes. It is here at the kinetochore where persistent attachments must be made to microtubules and maintained throughout mitosis to align and segregate chromosomes. The heterotetrameric Ndc80 complex has been demonstrated in many cell types to be essential for kinetochore-microtubule attachment. We aim to identify proteins that interact with Ndc80 complex proteins to coordinately regulate kinetochore-microtubule attachment in mitosis.