Cell Cycle
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.
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