The centrosome serves as the primary microtubule-organizing center of the cell and has a profound influence on all microtubule dependent processes. The interphase centrosome duplicates before mitosis and the daughter centrosomes define the two poles of the mitotic spindle. Our research is directed at elucidating the control mechanisms for cell division with an emphasis on learning more about the interrelationship between centrosomes and the cell cycle, particularly non-traditional activities of the centrosome. We analyze the functional properties of living cells to provide information that cannot be obtained by conventional means and that will set the stage for further biochemical or molecular studies. 1. We will complete and extend our work aimed at understanding how centrioles influence the ability of the cell to progress through GI. 2. Cells from which the centrosome has been laser ablated will reassemble multiple centrosomes during prolonged S phase. To test concerns that this is due to residual fragments of the original centrosome that """"""""seed"""""""" the assembly of new centrosomes, we will use mechanical microsurgery to remove the interphase centrosome and determine if truly new centrosomes can reassemble. 3. When mammalian somatic cells fail to cleave, they arrest in G1 if they have a functional p53 pathway. Cleavage failure is a critically important event to monitor because it leads to extra centrosomes and multipolar mitosis. This causes genomic instability that can contribute to the genesis of cancer. We will conduct a number of functional studies to determine how the cell knows that it is polyploid. 4. A key issue in centrosome biology is how human tumor cells develop the extra centrosomes that lead to genomic instability and genetic imbalances. Some hold that centrosome amplification is simply the consequence of cleavage failure while others claim that centrosomes can reduplicate during a single cell cycle. We will test if centrosomes can reduplicate within a cell cycle under conditions where cleavage failure is not a factor.
Showing the most recent 10 out of 58 publications
