Gamma tubulin ring complex in microtubule nucleation

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DESCRIPTION (provided by applicant): The long-term goal is to understand how the centrosome assembles and functions in animal cells. The centrosome is the major microtubule nucleating and organizing center that participates in organizing interphase cytoplasm and mitotic spindle poles. In mitosis, a bipolar spindle is organized efficiently from two centrosomes duplicated during S phase of the cell cycle. Recent studies suggested that mis-regulated centrosome duplication lead to mono- or multi-polar spindles and chromosome mis-segregation, linking cancer formation to centrosome dysfunction. Therefore, understanding the structure and function of the centrosome is relevant to human health. This grant seeks to study the mechanism of centrosome-mediated microtubule nucleation and centrosome assembly via studying a large protein complex, the gamma-tubulin ring complex (gammaTuRC) found at the centrosome. gammaTuRC is an important microtubule nucleator at the centrosome and it is required for centrosome assembly. In this granting period, we hope to understand 1) how gammaTuRC is assembled from multiple subunits, 2) how gammaTuRC functions in microtubule nucleation and organization, 3) how gammaTuRC is recruited to the centrosome to participate in microtubule nucleation and centrosome assembly.