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Walther Flemming and his contemporaries first described the process of mitotic cell division on the basis of microscopic observations over a century ago. In the ensuing 100-plus years, the disciplines of cell biology, genetics, biochemistry, and molecular biology have provided a detailed, yet incomplete, molecular view of the mechanics and regulation of eukaryotic cell division and its relationship to diseases such as cancer. Now, genomic and proteomic technologies offer new and powerful tools to enhance our understanding of this amazingly intricate and fundamental life process. Proteomic studies shed new light on cell division through the large-scale mapping of cell cycle–dependent protein modifications. These studies alter our perception of the complexity of the cell cycle and will serve as a framework for future research efforts to completely characterize the molecular mechanisms of its regulation.