Grant: Project Grant

Cancer is caused by cells that divide excessively. Errors in cell division lead to genomic alterations that contribute to a further loss of control over cell division. Chromosomes are contained in a nucleus delineated by a nuclear envelope comprising several important proteins that ensure structural integrity and intracellular communication. When a cell enters mitosis, the nuclear envelope breaks down to allow the sorting and partitioning of two identical sets of chromosomes in mitosis. After mitosis, the nuclear envelope must reassemble around chromosomes in an orderly manner. Defects in nuclear envelope reformation can lead to fragmented nuclei and DNA damage, which can accelerate cancer progression. However, the immune system is capable of detecting and destroying cells with defective nuclei. The molecular mechanisms by which the nuclear envelope reassembles and can become defective are not completely understood. As genes and mechanisms controlling cell division have been strongly conserved in evolution, we will take advantage of the powerful and versatile model that is the fruit fly Drosophila. We will use flies and fly cells in culture to dissect in details the mechanisms of nuclear envelope reformation after mitosis. We will also determine the biological consequences of defects in this process in different tissue types of the developing animal. The new knowledge will serve as a basis to understand how nuclear envelope reformation defects can impact cancer progression in humans. It may also suggest potential new therapeutic avenues. In particular, interfering with nuclear envelope reformation in dividing cancer cells could enhance their destruction of by the patient's immune system.