Essential Cell Biology 5th edition

616
CHAPTER 18
The Cell-Division Cycle
INJECT CYTOPLASM
FROM M-PHASE
CELL
spindle
easily detected
INJECT CYTOPLASM
FROM INTERPHASE
CELL
nucleus
oocyte
(A)
OOCYTE IS
DRIVEN INTO
M PHASE
(B)
OOCYTE
DOES NOT
ENTER
M PHASE
Figure 18−7 MPF activity was discovered by injecting Xenopus egg cytoplasm
into Xenopus oocytes. (A) A Xenopus oocyte is injected with cytoplasm taken from
a Xenopus egg in M phase. The cell extract drives the oocyte into M phase of the
first meiotic division (a process called maturation), causing the large nucleus to break
down and a spindle to form. (B) When ECB5 the E18.07/18.07
cytoplasm is instead taken from a cleaving
egg in interphase, it does not cause the oocyte to enter M phase. Thus, the extract in
(A) must contain some activity—a maturation promoting factor (MPF)—that triggers
entry into M phase.
Fishing in clams
M cyclin was initially identified by Tim Hunt as a protein
whose concentration rose gradually during interphase
and then fell rapidly to zero as cleaving clam eggs
went through M phase (see Figure 18−5). The protein
repeated this performance in each cell cycle. Its role in
cell-cycle control, however, was initially obscure. The
breakthrough occurred when cyclin was found to be a
component of MPF and to be required for MPF activity.
Thus, MPF, which we now call M-Cdk, is a protein complex
containing two subunits—a regulatory subunit, M
cyclin, and a catalytic subunit, the mitotic Cdk. After the
components of M-Cdk were identified, other types of
cyclins and Cdks were isolated, whose concentrations
or activities, respectively, rose and fell at other stages in
the cell cycle.
All in the family
While biochemists were identifying the proteins that
regulate the cell cycles of frog and clam embryos,
yeast geneticists—led by Lee Hartwell, studying baker’s
yeast (Saccharomyces cerevisiae), and Paul Nurse,
studying fission yeast (S. pombe)—were taking a genetic
approach to dissecting the cell-cycle control system. By
studying mutants that get stuck or misbehave at specific
points in the cell cycle, these researchers were able
to identify many genes responsible for cell-cycle control.
Some of these genes turned out to encode cyclin
or Cdk proteins, which were unmistakably similar—in
both amino acid sequence and function—to their counterparts
in frogs and clams. Similar genes were soon
identified in human cells.
Many of the cell-cycle control genes have changed so
little during evolution that the human version of the
gene will function perfectly well in a yeast cell. For
example, Nurse and colleagues were the first to show
that a yeast with a defective copy of the gene encoding
its only Cdk fails to divide, but it divides normally
if a copy of the appropriate human gene is artificially
introduced into the defective cell. Surely, even Darwin
would have been astonished at such clear evidence that
humans and yeasts are cousins. Despite a billion years
of divergent evolution, all eukaryotic cells—whether
yeast, animal, or plant—use essentially the same molecules
to control the events of their cell cycle.