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Cells normally divide in only two directions, so that each daughter cell gets the right genetic material, which is exactly half of the chromosomes. A structure called the centrosome controls this process. Dividing cells have two centrosomes that act as opposite poles and draw the dividing chromosomes toward them. Multiple centrosomes cause problems in cell division and lead to lengthy delays. We have found that irradiation, a commonly-used treatment in prostate cancer, leads to changes in how centrosomes are put together and in their number. We propose to explore how cells control the integrity of their centrosomes and thus control the number of centrosomes. We wish to test whether forcing prostate cancer cells to make more than the normal number of centrosomes will make them more sensitive to DNA damaging treatments, such as irradiation. We will explore how DNA damage-induced cell death occurs in cells that have experimentally-induced alterations in their centrosomes. Changes in the genetic makeup of cells are one of the key differences between cancer cells and normal cells. Instability in the genome is believed to be a key early event in cancer development and centrosome abnormalities are involved in how cancer arises. Our work will also examine how cells fragment their centrosomes or acquire the wrong number of these structures. Together, these findings will explore an important mechanism of cancer development as well as testing a potential new method to improve the selective killing of cancer cells.
The process of cell division is tightly controlled by centrosomes, which ensure that each daughter cell gets the correct number of chromosomes following cell division. The correct number of centrosomes in a dividing cell is two and the presence of multiple centrosomes can cause major problems in cell division. The aim of this project is to test whether forcing prostate cancer cells to make multiple centrosomes will make them more sensitive to certain cancer treatments, such as irradiation. Additionally, this study will investigate how exactly prostate cells acquire the wrong number of centrosomes.
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