The cell cycle entails an ordered series of macromolecular events that lead to cell division and the production of two daughter cells each containing chromosomes identical to those of the parental cell. Duplication of the parental chromosomes occurs during the S phase of the cycle, and one of the resulting daughter chromosomes is distributed to each daughter cell during mitosis. Precise temporal control of the events of the cell cycle ensures that the replication of chromosomes and their segregation to daughter cells occur in the proper order and with extraordinarily high fidelity. Regulation of the cell cycle is critical for the normal development of multicellular organisms, and loss of control ultimately leads to cancer, an all-too-familiar disease that kills one in every six people in the developed world.
In the late 1980s, it became clear that the molecular processes regulating the two key events in the cell cycle chromosome replication and segregation—are fundamentally similar in all eukaryotic cells. Because of this similarity, research with diverse organisms, each with its own particular experimental advantages, has contributed to a growing understanding of how these events are coordinated and controlled. Biochemical and genetic techniques, as well as recombinant DNA technology, have been employed in studying various aspects of the eukaryotic cell cycle. These studies have revealed that cell replication is primarily controlled by regulating the timing of nuclear DNA replication and mitosis. The master controllers of these events are a small number of heterodimeric protein kinases that contain a regulatory subunit (cyclin) and catalytic subunit (cyclindependent kinase).
These kinases regulate the activities of multiple proteins involved in DNA replication and mitosis by phosphorylating them at specific regulatory sites, activating some and inhibiting others to coordinate their activities. In this chapter we focus on how the cell cycle is regulated and the experimental systems that have led to our current understanding of these crucial regulatory mechanisms.