Porth's Essentials of Pathophysiology, 4e

75

Cell Proliferation and Tissue Regeneration and Repair

C h a p t e r 4

3

S

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. 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.

G 1

Stable cells (e.g., hepatocytes)

G 2

M

G 0

Permanent cells (e.g., nerves)

G 1 /S checkpoint (checks for DNA damage)

4

S

Cyclin E

G 1

Cyclin A

G 2

Cyclin B

M

G 0

G 2 /M checkpoint (checks for damaged or unduplicated DNA)