Abstract

This thesis explores the requirement of anillin, a cytokinesis regulator, in different human cell types and the mechanism that regulates anillin function. Cytokinesis is the process that physically separates a cell into two daughter cells. It takes place during mitotic exit to complete the cell cycle. Cytokinesis is spatiotemporally controlled to ensure that each daughter cell inherits the proper distribution of genomic and cytoplasmic content. Dysregulation of cytokinesis is correlated with diseases such as cancer. In metazoan cells, cytokinesis relies on the assembly and ingression of an actomyosin ring that pinches in the overlying membrane. Anillin is a scaffold protein with multiple binding partners that crosslinks the actomyosin ring to the membrane. Multiple conserved mechanisms regulate cytokinesis, and some mechanisms may be favored over others depending on the cell type. Our lab recently discovered a chromatin-based pathway that regulates ring assembly and position through anillin. We propose that this pathway is more strongly required in cancer cells with high aneuploidy, which typically arises during cancer progression. In support of this model, we found that anillin depletion causes a higher incidence of cytokinesis failure in cancer cells with higher aneuploidy. Using CRISPR-Cas9 to endogenously tag anillin, we define the thresholds of anillin required to support cytokinesis in different cell types. We also explored the mechanism regulating anillin function, and found that the chromatin pathway controls phospholipid binding required for the cortical recruitment of anillin. My findings revealed how the chromatin pathway controls the molecular function of anillin for cytokinesis.