C h a p t e r 4
Cell Proliferation and Tissue Regeneration and Repair
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Permanent cells
(e.g., nerves)
M
G
1
G
2
S
G
0
Stable cells
(e.g.,
hepatocytes)
Gap 0.
G
0
is the stage after mito-
sis during which a cell may leave the
cell cycle and either remain in a state
of inactivity or reenter the cell cycle
at another time. Labile cells, such as
blood cells and those that line the
gastrointestinal tract, do not enter
G
0
but continue cycling. Stable cells,
such as hepatocytes, enter G
0
after
mitosis but can reenter the cell cycle
when stimulated by the loss of other
cells. Permanent cells, such as neu-
rons that become terminally differ-
entiated after mitosis, leave the cell
cycle and are no longer capable of
cell renewal.
3
M
G
1
G
2
S
G
0
G
1
/S checkpoint
(checks for DNA damage)
G
2
/M checkpoint
(checks for damaged
or unduplicated DNA)
Cyclin E
Cyclin A
Cyclin B
Checkpoints and Cyclins.
In
most cells there are several check-
points in the cell cycle, at which time
the cycle can be arrested if previous
events have not been completed. For
example, the G
1
/S checkpoint moni-
tors whether the DNA in the chro-
mosomes is damaged by radiation
or chemicals, and the G
2
/M check-
point prevents entry into mitosis if
DNA replication is not complete.
The cyclins are a family of pro-
teins that control entry and progres-
sion of cells through the cell cycle.
They function by activating pro-
teins called cyclin-dependent kinases
(CDKs). Different combinations of
cyclins and CDKs are associated
with each stage of the cell cycle. In
addition to the synthesis and deg-
radation of the cyclins, the cyc-
lin–CDK complexes are regulated
by the binding of CDK inhibitors.
The CDK inhibitors are particularly
important in regulating cell cycle
checkpoints during which mistakes
in DNA replication are repaired.
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