390
Cell Nucleus Biogenesis, Structure and Function
CycB
CDC2
CycA
CDK2
CycE
CDK2
CycD
CDK4
CycD
CDK6
G0
Quiescence
HDAC
pRB
pRB
E2F
E2F
P
P
P
P21, p27
cip/kip
p16
INK4a
G2
G1
M
S
Start
Fig. 2
The cell cycle. In proliferating mammalian cells, the cell cycle
covers roughly 24 h. This growth cycle is depicted by the central ring, in
which the amount of DNA in the cell is depicted (relative intensity of blue
shading). The notable events of this cycle are the S-phase where DNA is
replicated and the M-phase where chromosome segregation and daughter
cell formation take place. These are separated by two gap phases – G1 and
G2. Progression through the cell cycle is dictated by mitogenic signals
from growth factors that interact with the cell cycle machinery, the critical
components of which are shown here. Cyclin/CDK/C complexes drive the
cycle. Kinase activities within the CDK proteins are responsible for
regulating the downstream effects and the activity of the kinases is
regulated by the cell cycle dependent expression of the cyclin proteins. The
cell cycle machinery has many targets. For simplicity, the ±gure shows one
major target, the cell cycle regulator Rb. Rb is phosphorylated by the cell
cycle kinases and this activity releases Rb from complexes that suppress
the transcription of critical proteins involved in proliferation, particularly
DNA synthesis. Once Rb phosphorylation has activated this process, a cell
is committed to pass through the cycle and on to mitosis. The activity of
the cell cycle proteins is regulated by numerous other interactions such as
those with the tumor suppressor proteins p21 and p16
INK4a
. (See color
plate p. xxix).
to generate two daughter cells, mito-
sis can begin. The onset of mitosis is
driven by the cdc2/cyclinB complex. Major
phosphorylation targets for this complex
include histone H1 and lamin proteins.
ModiFcation of these proteins, together
with numerous other modiFcations, drive
chromosome condensation and disruption
of the nuclear membrane. RNA synthesis
is also switched off. Chromosome con-
densation begins late in G2; at this stage
of the cell cycle, simple staining of DNA
within the nuclei reveals the wormlike
appearance of the condensing chromatin.
The condensation process involves an axial
retraction of the chromatin loops and
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