The ability to reproduce is a defining feature of all living things. The earliest forms of life — little more than complex molecules suspended in primeval soup — were capable of duplicating themselves. In the billions of years that have passed since then, those simple beings evolved into the complex, diverse and beautiful forms that surround us today, and throughout that time reproduction has remained a central feature of life and a key to its success.
The cell is the building block of all life on this planet, and cell reproduction is therefore essential for the continued existence of all living things. Single-celled organisms depend on cell reproduction to generate an entire new organism, and cell reproduction is therefore essential for the long-term survival and evolution of that organism as a species. Multicellular organisms depend on cell reproduction for many important additional functions. During the growth and development of these organisms, countless new cells are needed to produce the diverse communities of cells that make up the tissues and organs. In the adult, new cells must be produced when tissues grow, or to replace cells that die from natural causes or are lost to environmental damage. Thus, life as we know it is inconceivable without mechanisms for the rapid production of new cells.
All cells reproduce by the duplication and division of pre-existing cells. This process depends on an orderly sequence of events, called the cell cycle, in which the cell duplicates its contents and then divides in two. A key feature of the cell cycle is that it leads to the accurate distribution of the cell’s genetic information to the next generation. To produce two genetically identical daughter cells, the DNA in each cell — carried on the chromosomes —is replicated to produce two complete and accurate copies. Chromosome duplication occurs in the S phase of the cell cycle. In M phase, the duplicated chromosomes are segregated to the two daughter cells, so that each receives a copy of the entire genome.
Progression through the stages of the cell cycle is governed by a complex regulatory system that triggers cell cycle events in the correct sequence and ensures that those events are coordinated with each other. Our research focuses on understanding the components and operations of the cell cycle control system. We study this problem primarily in the budding yeast Saccharomyces cerevisiae, but our findings have broad significance for human diseases, such as cancer, that arise from defects in cell proliferation or chromosome segregation.
Our general strategy is to use quantitative biochemical analysis to understand the detailed mechanisms of key enzymes involved in cell cycle control. We also employ molecular genetics, proteomics, advanced light microscopy, and computational methods to explore how these enzymes are assembled into a robust regulatory system that drives accurate cell cycle progression. Our work centers on two regulatory enzymes: the cyclin-dependent protein kinases (Cdks) and a ubiquitin ligase called the Anaphase-Promoting Complex (APC). We focus primarily on the roles of these enzymes during chromosome segregation in M phase.