Project 462673

Cell division is a fundamental process for all living organisms on Earth, and its dysregulation can lead to developmental abnormalities (for instance trisomies) or disease (such as cancer). The last step of cell division, cytokinesis - the process that separates the two daughter-cells - must be highly regulated to avoid division failure, which can lead to tumour formation. However, regulated cytokinesis incompletion is desired in some tissues, in which it leads to the development of a specific architecture where cells remain stably interconnected, called a syncytium. This is the case for the gametes (also called germ cells) of most animals, including our choice model, the small worm C. elegans. In a previous study, we identified several regulators important to regulate C. elegans germ cell cytokinesis incompletion, including the well known cytokinesis protein RhoA, as well as OSGN-1, a protein with an uncharacterized function. Our preliminary analysis suggests that OSGN-1 is an enzyme that controls the activity of RhoA by catalyzing the addition of one or more atoms of oxygen onto specific regions of the protein, and that human cells have two similar proteins (OSGIN1 and OSGIN2) that do the same thing. We herein propose to characterize in detail this oxygen transfer function of OSGN-1 and determine if one or both human form(s) of this protein performs the same function in human cells. This study will provide important information on a novel protein that impacts RhoA activity in normal conditions and may improve our understanding on how deregulated cytokinesis eventually leads to cancer.