Successful traversal of the cell division cycle is paramount for maintaining a cell's genomic integrity and fitness. To ensure the faithful replication and segregation of the genome, cellular components, and cytoplasm, eukaryotes have evolved a complex cell cycle, with layers of regulation and built-in checkpoints. Disruption of any of these processes can be catastrophic for the cell or organism, often resulting in deleterious mutations or cell death. As deletion/improper activation of key regulatory proteins has been shown to be involved in tumorigenesis, a full understanding of the cell cycle machinery is of vital importance.;The work presented here seeks to investigate the cell cycle using three different methods. First, I used existing cell cycle data to further investigate the function of the gene FAM64A, which I hypothesized would play a role in maintaining or establishing the mitotic spindle. Fam64A was identified as showing peak mRNA expression in G2/M phase in genome-wide expression data; I further showed that the protein was also cell cycle-regulated, and was degraded by the proteasome at the end of mitosis. I report that the knockdown of Fam64A by siRNA results in monopolar spindles. Functionally, Fam64A interacts with members of the Chromosomal Passenger Complex (CPC) and other key mitotic regulators in vivo.;I also sought to identify the full complement of cell cycle-regulated genes in an untransformed cell line, Immortalized Mammary Epithelial Cells (IMECs). While there exist studies identifying cell cycle-regulated genes, often these are performed in tumor-derived cell lines, and here I report that the genes identified as cell cycle-regulated in IMECs are quite divergent from those reported in HeLa cells, suggesting that genes required for cell cycle progression may vary between cells of different lineages and transformation status.;Finally, I performed a meta-analysis of existing large-scale and genome-wide screens for genes required for cell cycle progression. I found that the overlap between four published screens was very small, with only Polo-like kinase 1 being identified as having a cell cycle phenotype in all four screens. This underscores the need for more of such screens using a variety of cell lines and techniques. With the collation of many similar screens, I may achieve a much more complete understanding of the many proteins required for cell cycle progression, and with that, perhaps future targets for cancer therapies.
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