copyright © 2005 pearson education, inc. publishing as benjamin cummings frequency of cell division...

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Frequency of Cell Division

• Varies from cell to cell

– Skin cells divide frequently

– Liver cells only when needed

– Nerve & muscle cells do NOT divide


What drives the cell cycle?

• The cell cycle is driven by specific molecular signals present in the cytoplasm


Cell cycle control system

• Molecules in the cell trigger and coordinate key events in the cell cycle

• Compared to the control system on an automatic washing machine

• Cell cycle is regulated at certain checkpoints by both internal and external controls

• Checkpoint = critical control point where stop & go ahead signals are given


Checkpoints

• G1, G2, and M phases

• G1 is the most important “restriction point”

– If the go ahead signal is given the cell usually completes S, G2 and M phases

– If the go ahead signal is NOT given it enters into a nondividing state called G0


Figure 12.14 Mechanical analogy for the cell cycle control system

Control system

G2 checkpoint

M checkpoint

G1 checkpoint

G1

S

G2M


Figure 12.15 The G1 checkpoint

G1 checkpoint

G1G1

G0

(a) If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

(b) If a cell does not receive a go-ahead signal at the G1checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.


Regulatory molecules of the cell cycle

• Kinases and cyclins

• Proteins kinases give the go ahead signals at the G1 & G2 checkpoints by phosphorylation

• These kinases are always present but in order to be active they must be attached to a cyclin

• Called Cyclin Dependent kinases (Cdks)

• Fluctuation of MPF (M-phase promoting factor)

• Both Cdk and cyclin are needed to get past the G2 checkpoint


Figure 12.16 Molecular control of the cell cycle at the G2 checkpoint

Accumulated cyclin moleculescombine with recycled Cdk mol-ecules, producing enough molecules of MPF to pass the G2 checkpoint and initiate the events of mitosis.

MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase.

3

During G1, conditions in the cell favor degradation of cyclin, and the Cdk component of MPF is recycled.

5

During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G1 phase.

4

2

Synthesis of cyclin begins in late S phase and continues through G2. Because cyclin is protected from degradation during this stage, it accumulates.

1

Cdk

CdkG2

checkpoint

CyclinMPF

Cyclin is degraded

DegradedCyclin

G 1

G 2

S

M

G1G1 S G2 G2SM M

MPF activity

Cyclin

Time

(a) Fluctuation of MPF activity and cyclin concentration during the cell cycle

(b) Molecular mechanisms that help regulate the cell cycle

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cen

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Other factors affecting cell division

• Growth factors – a protein that is released by certain cells that stimulate other cells to divide

• Density-dependent inhibition – when it gets too crowded cells will stop dividing because there is not enough nutrients to support more

• Anchorage dependence – cells must be attached to something in order to divide


Loss of cell cycle control – Cancer cells

• Cancer cells do not respond normally to the body’s control mechanisms

– Do not exhibit density-dependent inhibition

– Do not stop growing when growth factors are depleted

• Why??

– Maybe they don’t need growth factors or make their own, abnormality in the checkpoints are some of the hypothesis


Cancer in the body

• Transformation – converts a normal cell into a cancer cell

• Normally our body recognizes it & destroys it but sometimes they evade destruction, multiply and form a tumor (mass or lump)

• If the cells remain at the original site the mass is said to be benign

• If the cells move & cause organ damage it is said to be malignant


Malignant tumor cells

• Abnormal in many ways

– Unusual number of chromosomes

– Metabolisms are disabled

– Lose or destroy attachments to neighbor cells

– Secrete signals that cause blood vessels to grow toward them

– Some can travel in blood and lymph to other parts of the body (metastasis)


Treatment of cancer cells

• Localized tumors – radiation (damages DNA in cancer cells more than normal cells)

• Metastatic tumors – chemotherapy is used (drugs that are toxic to actively dividing cells)

– Taxol – freezes the mitotic spindle by preventing microtubule depolymerization which stops actively dividing cells from going past metaphase

– Sickness, hair loss, nausea result from these drugs effects on healthy cells

copyright © 2005 pearson education, inc. publishing as benjamin cummings frequency of cell division...

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