Essential Cell Biology 5th edition

The Cell-Cycle Control System
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ensures that the duplicated chromosomes are properly attached to a
cytoskeletal machine, called the mitotic spindle, before the spindle pulls
the chromosomes apart and segregates them into the two daughter cells.
In animals, the transition from G 1 to S phase is especially important as a
point in the cell cycle where the control system is regulated. Signals from
other cells stimulate cell proliferation when more cells are needed—and
block it when they are not. The cell-cycle control system therefore plays
a central part in the regulation of cell numbers in the tissues of the body;
if the control system malfunctions such that cell division is excessive,
cancer can result. We discuss later how extracellular signals influence the
decisions made at the G 1 -to-S transition.
Cell-Cycle Control Is Similar in All Eukaryotes
Some features of the cell cycle, including the time required to complete
certain events, vary greatly from one cell type to another, even within the
same organism. The basic organization of the cycle, however, is essentially
the same in all eukaryotic cells, and all eukaryotes appear to use
similar machinery and control mechanisms to drive and regulate cellcycle
events. The proteins of the cell-cycle control system first appeared
more than a billion years ago, and they have been so well conserved
over the course of evolution that many of them function perfectly when
transferred from a human cell to a yeast (see How We Know, pp. 30−31).
Because of this similarity, biologists can study the cell cycle and its regulation
in a variety of organisms and use the findings from all of them
to assemble a unified picture of how the cycle works. Many discoveries
about the cell cycle have come from a systematic search for mutations
that inactivate essential components of the cell-cycle control system
in yeasts. Likewise, studies of both cultured mammalian cells and the
embryos of frogs and sea urchins have been critical for examining the
molecular mechanisms that underlie the cycle and its control in multicellular
organisms like ourselves.
THE CELL-CYCLE CONTROL SYSTEM
Two types of machinery are involved in cell division: one manufactures
the new components of the growing cell, and another hauls the components
into their correct places and partitions them appropriately when
the cell divides in two. The cell-cycle control system switches all this
machinery on and off at the correct times, thereby coordinating the various
steps of the cycle. The core of the cell-cycle control system is a series
of molecular switches that operate in a defined sequence and orchestrate
the main events of the cycle, including DNA replication and the segregation
of duplicated chromosomes. In this section, we review the protein
components of the control system and discuss how they work together to
trigger the different phases of the cycle.
The Cell-Cycle Control System Depends on Cyclically
Activated Protein Kinases Called Cdks
The cell-cycle control system governs the cell-cycle machinery by
cyclically activating and then inactivating the key proteins and protein
complexes that initiate or regulate DNA replication, mitosis, and cytokinesis.
This regulation is carried out largely through the phosphorylation
and dephosphorylation of proteins involved in these essential processes.
As discussed in Chapter 4, phosphorylation followed by dephosphorylation
is one of the most common ways by which cells switch the activity of
a protein on and off (see Figure 4−46), and the cell-cycle control system