John Cooper

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  The Function of Dynein in Budding Yeast: Mechanism, Regulation and Checkpoint Activity
  John Cooper
  I will discuss work from our lab and other labs on how dynein functions to position the mitotic spindle and the nucleus in budding yeast. Interactions of cytoplasmic microtubules with the cortex control spindle position, and dynein represents one of the major pathways by which spindle position is controlled. Dynein functions by an "offloading" mechanism in which dynein targeted to dynamic microtubule plus ends is transferred to the cortex, where it is anchored and activated for minus-end directed motor activity, which pulls the spindle into the neck between mother and bud. Dynein is a multi-subunit complex, and dynein requires the function of dynactin, another multisubunit complex. Other factors are important for dynein targeting, both to the plus end and to the cortex. Dynein appears to be regulated spatially and temporally, during the course of its action. Finally, loss of dynein function and failure to properly position the spindle leads to activation of a cell-cycle checkpoint, which delays the progression of the cell cycle until alternative mechanisms are able to move the spindle into the mother / bud neck. The mechanism of this checkpoint relies on feedback information from cytoplasmic microtubules, based on new laser-cutting experiments.