Greehey CCRI Seminar Series: Katsumi Kitagawa, Pharm.D., PhD (UTHSA)
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The molecular mechanisms that ensure accurate chromosome segregation in mitosis and meiosis are fundamental to conserving eukaryotes’ euploidy. Errors in this process (e.g., chromosome nondisjunction and chromosome loss) result in aneuploidy—the phenotypic consequences of which are usually profound, including cancer, birth defects, and developmental disorders such as Down syndrome. In humans, errors in chromosome segregation may trigger the onset of neoplasia by uncovering the expression of recessive oncogenic phenotypes or contributing to the development of specific aneuploidies. The centromere, a single locus per chromosome, is essential to ensure high fidelity of chromosome transmission. The kinetochore (the protein complex at the centromere) mediates the attachment of chromosomes to spindle microtubules and directs chromosome movement during mitosis. Cells have a surveillance system, the spindle checkpoint, which can delay mitotic progression by transiently inhibiting the anaphase-promoting complex in response to the defective kinetochore-microtubule attachment—defects in kinetochore function and the spindle checkpoint, resulting in aneuploidy. Considerable evidence indicates a role of a dysfunctional spindle checkpoint in tumorigenesis.