CH 12 The Cell Cycle

Why cell division?

1. Single cell organisms reproduce this way.2. Multicellular Organisms

a. Need this to grow from a fertilized egg (200trillion)

b. Need this to repair after grown

I. Cell Division BasicsA. Organizing Genetic Material

1. Genome: All the genetic info. of a cell.a. After cell division each daughter cell must get the same

genome.

2. Chromosomes: A condensed form of DNA found during cell division.

a. Humans have 46 chromosomes. (23 from each parent)b. This condensed form of organizes the DNA for division.

B. Distributing Chromosomes During Cell Division1. Chromatin: A complex of DNA and protein 2. In preparation for cell division chromatin

coils into chromosomes.a. Each chromosome is made of 2 sister

chromatids. (identical)b. Centromere: holds the sisters

together.

1. Mitosis: Division of nucleusa. Produces all somatic cells: all body cells (46 chromosomes)b. Not used to make gametes: Reproductive cells (23

chromosomes)

2. Cytokinesis: Division of cytoplasm that follows mitosis.

II. MitosisA. Phases of the cell cycle

1. Interphase (90%): Growth time that has 3 partsa. G1: Cell grows and makes proteinsb. S: Cell grows, makes proteins, and copies DNAc. G2: Cell grows and makes proteins

INTERPHASE

G1

S(DNA synthesis)

G2Cyto

kines

is

Mito

sis

MITOTIC(M) PHASE

Figure 12.5

2. Mitosis: Dividing the nucleus and evenly distributing the DNA to the daughter cells.a. Prophase:

• Chromatin fibers begin to tightly coil to make observable chromosomes.

• Spindle begins to form. Made of centrosomes and microtubules• Centrosomes start to move away from each other.

G2 OF INTERPHASE

PROPHASE PROMETAPHASECentrosomes(with centriole pairs) Chromatin

(duplicated)

Early mitoticspindle

AsterCentromere

Fragmentsof nuclearenvelope

Kinetochore

Nucleolus Nuclearenvelope

Plasmamembrane

Chromosome, consistingof two sister chromatids

Kinetochore microtubule Figure 12.6

Nonkinetochoremicrotubules

b. Prometaphase:• Nuclear envelope fragments• Centrosomes reach poles and microtubules reach to

chromosomes• Kinetochores develop at the centromere of each chromosome

G2 OF INTERPHASE

PROPHASE PROMETAPHASE

Centrosomes(with centriole pairs) Chromatin

(duplicated)

Early mitoticspindle

Aster

CentromereFragmentsof nuclearenvelope

Kinetochore

Nucleolus Nuclearenvelope

Plasmamembrane

Chromosome, consistingof two sister chromatids

Kinetochore microtubule

Nonkinetochoremicrotubules

c. Metaphase:• Centrosomes at opposite ends of cell• The chromosomes move to the metaphase plate (equator)• The kinetochores of each chromatid are attached to a

microtubule coming from opposite polesd. Anaphase:

• Sister chromatids are pulled apart by microtubules• Each chromatid travels toward opposite poles

Centrosome at one spindle pole

Daughter chromosomes

METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS

Spindle

Metaphaseplate Nucleolus

forming

Cleavagefurrow

Nuclear envelopeforming

Figure 12.6

e. Telophase:• Two nuclear envelopes start to form around chromosomes at each

pole• Chromosomes start to uncoil

3. Cytokinesis: Division of the cytoplasma. Starts during telophaseb. Cleavage furrow develops and pinches cell in two.

Centrosome at one spindle pole

Daughter chromosomes

METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS

Spindle

Metaphaseplate Nucleolus

forming

Cleavagefurrow

Nuclear envelopeforming

Figure 12.6

III. Cell Cycle ControlA. The cell cycle is regulated by a molecular system.

1. The regulating molecules are found in the cytoplasm.

In each experiment, cultured mammalian cells at two different phases of the cell cycle were induced to fuse.

When a cell in the M phase was fused with a cell in G1, the G1 cell immediately began mitosis— a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.

EXPERIMENTS

RESULTS

CONCLUSION The results of fusing cells at two different phases of the cell cycle suggest that molecules present in the cytoplasm of cells in the S or M phase control the progression of phases.

When a cell in the S phase was fused with a cell in G1, the G1 cellimmediately entered the S phase—DNA was synthesized.

S

S S M M

MG1 G1

Experiment 1 Experiment 2

Figure 12.13 A, B

B. Cell cycle control System: A set of molecules that trigger events in the cell cycle.

1. Checkpoint: A control point where stop and go signals can regulate the cycle.a. Checkpoints respond to both internal and external controls.b. Most checkpoints stop cell cycle untill overridden by a signal.c. Checkpoints are located at G1, G2, and M phases.

Figure 12.14

Control system

G2 checkpointM checkpoint

G1 checkpoint

G1

S

G2M

2. G1 The most important checkpoint.a. If G1 receives a signal, all of cell cycle will continue.

b. If G1 does not receive the signal, the cell will enter G0 phase, a nondividing state.

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.

Figure 12.15 A, B

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

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

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 MMPF activity

Cyclin

Time

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

(b) Molecular mechanisms that help regulate the cell cycle

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

3

Figure 12.16 A, B

M

C. How cycle control works1. Kinases: Enzymes that activate or inactivate other proteins by

phosphorylating them.a. They give the go-ahead at G1 and G2 checkpoints.

2. Cyclins: Activate the kinases.3. The cell produces cyclins to activate the kinases which override

the stop points.

D. Internal and External Signals:1. Internal Signals: based on internal happenings.

a. Anaphase Signal: • kinetichores that are unattached to spindles send a signal

that holds sister chromatids together.• When all kinetichores are attached to a spindle, the signal

stops and sister chromatids are allowed to separate.

2. External Signals: Based on cell surroundingsa. Growth Factors: a protein released by one cell that

stimulates another cell to divide. • Platelet example after an injury.

b. Density-Dependent Inhibition: When cells get crowded they stop dividing.

c. Anchorage Dependence: Cells won’t divide unless they are attached to something.

Cells anchor to dish surface anddivide (anchorage dependence).

When cells have formed a complete single layer, they stop dividing (density-dependent inhibition).

If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition).

Normal mammalian cells. The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer.

(a)

25 µmFigure 12.18 A

E. Cancer: Loss of cell cycle control1. Why cancer cells are different

a. No density-dependent inhibitionb. Don’t need growth factorsc. If they stop dividing it is at random places.d. Have the ability to divide forevere. Often secrete signals to tell blood vessels to grow toward the tumor.f. May have abnormal numbers of chromosomes.

25 µm

Cancer cells do not exhibitanchorage dependence or density-dependent inhibition.

Cancer cells. Cancer cells usually continue to divide well beyond a single layer, forming a clump of overlapping cells.

(b)

Figure 12.18 B

2. Transformation: The conversion of a normal cell to a cancer cell.a. Usually recognized and killed by the body.b. If not killed will lead to a tumor.

3. Benign Tumor: If cells remain localized to the tumor.4. Malignant Tumor: If cells start to invade other locations.

a. Metastasis: Spread of cancer cells.

5. Treatment of cancera. Radiation: Used on localized tumors.

• Damages cancer cells more than normal cells.• The cancer cells have lost ability to repair the damage.

b. Chemotherapy: Used on metastatic tumors.• The drugs interfere with steps of cell cycle.• Are harsh b/c they also interfere with normal cells.