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All organisms have mechanisms to ensure that cells produced from mitotic and meiotic divisions contain the proper number of chromosomes. The cell monitors that chromosomes are copied exactly once and then distributed correctly to daughter cells. This is critical since cells containing an incomplete chromosome complement will either die or have abnormal growth phenotypes. In humans, inaccurate chromosome segregation during mitosis is associated with cancer; inaccurate chromosome segregation in meiosis is associated with spontaneous miscarriage, as well as genetic defects such as Downs (trisomy 21). Many of the proteins and pathways that ensure accurate chromosome segregation are evolutionarily conserved from budding yeast to man. My research program takes advantage of the yeast model system and uses genomics, genetics, molecular biology, and biochemistry to study processes that contribute to the fidelity of chromosome distribution, in particular, 1) the cohesin pathway and 2) centromeric chromatin. The cohesin pathway The cohesin pathway is important to ensure that sister chromatids remain together until they are required to separate into daughter cells at the metaphase-to-anaphase transition. More recently, the cohesin pathway has been shown to contribute to the repair of DNA double-strand breaks and gene regulation. Mutations in the cohesin pathway have been associated with human diseases termed cohesinopathies. Our hypothesis is that the cohesin pathway participates in chromatin organization in the nucleus which can affect not only chromosome segregation but gene regulation and recombination. We are conducting experiments to test this hypothesis. Centromeric chromatin Eukaryotic cells contain a specialized histone variant that is incorporated into nucleosomes specifically at centromeres. This variant, known as Cse4 in budding yeast and more generally as CENP-A, is essential for marking the spot for kinetochore formation. Microtubules attach to kinetochores and help segregate chromosomes upon cell division. If any part of this process goes awry, the spindle checkpoint is activated. We are interested in how Cse4-containing chromatin is established and maintained in the genome. We have identified a Cse4-interacting protein, Scm3, as one factor that contributes to the formation and maintenance of centromeric chromatin. We have also identified additional Cse4-interacting factors that we have yet to characterize. We are actively pursuing experiments that will help us understand how proteins that associate with Cse4 participate in the formation of centromeric chromatin, the kinetochore, and the spindle checkpoint. Academic Appointment: Associate Professor, Department of Biochemistry & Molecular Biology, The University of Kansas School of Medicine Selected publications |
Gerton
Lab