Chapter 12

The Cell Cycle

• Overview: The Key Roles of Cell Division
• The continuity of life
• Is based upon the reproduction of cells, or cell division

Figure 12.1

• Unicellular organisms
• Reproduce by cell division

100 µm

(a) Reproduction. An amoeba, �a single-celled eukaryote, is �dividing into two cells. Each �new cell will be an individual�organism (LM).

Figure 12.2 A

• Multicellular organisms depend on cell division for
• Development from a fertilized cell
• Growth
• Repair

20 µm

200 µm

(b) Growth and development. �This micrograph shows a �sand dollar embryo shortly �after the fertilized egg divided, �forming two cells (LM).

(c) Tissue renewal. These dividing �bone marrow cells (arrow) will �give rise to new blood cells (LM).

Figure 12.2 B, C

• The cell division process
• Is an integral part of the cell cycle

• Concept 12.1: Cell division results in genetically identical daughter cells
• Cells duplicate their genetic material
• Before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA

Cellular Organization of the Genetic Material

• A cell’s endowment of DNA, its genetic information
• Is called its genome

• The DNA molecules in a cell
• Are packaged into chromosomes

50 µm

Figure 12.3

• Eukaryotic chromosomes
• Consist of chromatin, a complex of DNA and protein that condenses during cell division
• In animals
• Somatic cells have two sets of chromosomes
• Gametes have one set of chromosomes

Distribution of Chromosomes During Cell Division

• In preparation for cell division
• DNA is replicated and the chromosomes condense

• Each duplicated chromosome
• Has two sister chromatids, which separate during cell division

0.5 µm

Chromosome�duplication�(including DNA �synthesis)

Centromere

Separation �of sister �chromatids

Sister�chromatids

Centromeres

Sister chromatids

A eukaryotic cell has multiple�chromosomes, one of which is �represented here. Before �duplication, each chromosome�has a single DNA molecule.

Once duplicated, a chromosome�consists of two sister chromatids�connected at the centromere. Each�chromatid contains a copy of the �DNA molecule.

Mechanical processes separate �the sister chromatids into two�chromosomes and distribute �them to two daughter cells.

Figure 12.4

• Eukaryotic cell division consists of
• Mitosis, the division of the nucleus
• Cytokinesis, the division of the cytoplasm
• In meiosis
• Sex cells are produced after a reduction in chromosome number

• Concept 12.2: The mitotic phase alternates with interphase in the cell cycle
• A labeled probe can reveal patterns of gene expression in different kinds of cells

Phases of the Cell Cycle

• The cell cycle consists of
• The mitotic phase
• Interphase

INTERPHASE

G₁

S�(DNA synthesis)

G₂

Cytokinesis�Mitosis

MITOTIC�(M) PHASE

Figure 12.5

• Interphase can be divided into subphases
• G₁ phase
• S phase
• G₂ phase

• The mitotic phase
• Is made up of mitosis and cytokinesis

• Mitosis consists of five distinct phases
• Prophase
• Prometaphase

G₂ OF INTERPHASE

PROPHASE

PROMETAPHASE

Centrosomes�(with centriole pairs)

Chromatin�(duplicated)

Early mitotic�spindle

Aster

Centromere

Fragments�of nuclear�envelope

Kinetochore

Nucleolus

Nuclear�envelope

Plasma�membrane

Chromosome, consisting�of two sister chromatids

Kinetochore�microtubule

Figure 12.6

Nonkinetochore�microtubules

• Metaphase
• Anaphase
• Telophase

Centrosome at �one spindle pole

Daughter �chromosomes

METAPHASE

ANAPHASE

TELOPHASE AND CYTOKINESIS

Spindle

Metaphase�plate

Nucleolus�forming

Cleavage�furrow

Nuclear �envelope�forming

Figure 12.6

The Mitotic Spindle: A Closer Look

• The mitotic spindle
• Is an apparatus of microtubules that controls chromosome movement during mitosis

• The spindle arises from the centrosomes
• And includes spindle microtubules and asters

• Some spindle microtubules
• Attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate

Centrosome

Aster

Sister�chromatids

Metaphase�Plate

Kinetochores

Overlapping�nonkinetochore�microtubules

Kinetochores microtubules

Centrosome

Chromosomes

Microtubules

0.5 µm

1 µm

Figure 12.7

• In anaphase, sister chromatids separate
• And move along the kinetochore microtubules toward opposite ends of the cell

EXPERIMENT

​

1 The microtubules of a cell in early anaphase were labeled with a fluorescent dye �that glows in the microscope (yellow).

Spindle�pole

Kinetochore

Figure 12.8

• Nonkinetechore microtubules from opposite poles
• Overlap and push against each other, elongating the cell
• In telophase
• Genetically identical daughter nuclei form at opposite ends of the cell

Cytokinesis: A Closer Look

• In animal cells
• Cytokinesis occurs by a process known as cleavage, forming a cleavage furrow

Cleavage furrow

Contractile ring of �microfilaments

Daughter cells

100 µm

(a) Cleavage of an animal cell (SEM)

Figure 12.9 A

• In plant cells, during cytokinesis
• A cell plate forms

Daughter cells

1 µm

Vesicles�forming �cell plate

Wall of �patent cell

Cell plate

New cell wall

(b) Cell plate formation in a plant cell (SEM)

Figure 12.9 B

• Mitosis in a plant cell

1

Prophase. �The chromatin�is condensing. �The nucleolus is �beginning to �disappear.�Although not �yet visible �in the micrograph, �the mitotic spindle is �staring to from.

Prometaphase.�We now see discrete�chromosomes; each �consists of two �identical sister �chromatids. Later�in prometaphase, the �nuclear envelop will �fragment.

Metaphase. The �spindle is complete,�and the chromosomes,�attached to microtubules�at their kinetochores, �are all at the metaphase �plate.

Anaphase. The�chromatids of each �chromosome have �separated, and the �daughter chromosomes�are moving to the ends �of cell as their �kinetochore�microtubles shorten.

Telophase. Daughter�nuclei are forming. �Meanwhile, cytokinesis�has started: The cell�plate, which will �divided the cytoplasm �in two, is growing �toward the perimeter �of the parent cell.

2

3

4

5

Nucleus

Nucleolus

Chromosome

Chromatine�condensing

Figure 12.10

Binary Fission

• Prokaryotes (bacteria)
• Reproduce by a type of cell division called binary fission

• In binary fission
• The bacterial chromosome replicates
• The two daughter chromosomes actively move apart

Origin of

replication

E. coli cell

Bacterial

Chromosome

Cell wall

Plasma

Membrane

Two copies

of origin

Origin

Origin

Chromosome replication begins.

Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell.

1

Replication continues. One copy of�the origin is now at each end of �the cell.

2

Replication finishes. The plasma membrane grows inward, and

new cell wall is deposited.

3

Two daughter cells result.

4

Figure 12.11

The Evolution of Mitosis

• Since prokaryotes preceded eukaryotes by billions of years
• It is likely that mitosis evolved from bacterial cell division
• Certain protists
• Exhibit types of cell division that seem intermediate between binary fission and mitosis carried out by most eukaryotic cells

• A hypothetical sequence for the evolution of mitosis

Most eukaryotes. In most other eukaryotes, including plants and animals, the spindle forms outside the nucleus, and the nuclear envelope breaks down during mitosis. Microtubules separate the chromosomes, and the nuclear envelope then re-forms.

Dinoflagellates. In unicellular protists called dinoflagellates, the nuclear envelope remains intact during cell division, and the chromosomes attach to the nuclear envelope. Microtubules pass through the nucleus inside cytoplasmic tunnels, reinforcing the spatial orientation of the nucleus, which then divides in a fission process reminiscent of bacterial division.

Diatoms. In another group of unicellular protists, the diatoms, the nuclear envelope also remains intact during cell division. But in these organisms, the microtubules form a spindle within the nucleus. Microtubules separate the chromosomes, and the nucleus splits into two daughter nuclei.

Prokaryotes. During binary fission, the origins of the daughter chromosomes move to opposite ends of the cell. The mechanism is not fully understood, but proteins may anchor the daughter chromosomes to specific sites on the plasma membrane.

(a)

(b)

(c)

(d)

Bacterial

chromosome

Microtubules

Intact nuclear

envelope

Chromosomes

Kinetochore

microtubules

Intact nuclear

envelope

Kinetochore

microtubules

Fragments of

nuclear envelope

Centrosome

Figure 12.12 A-D

• Concept 12.3: The cell cycle is regulated by a molecular control system
• The frequency of cell division
• Varies with the type of cell
• These cell cycle differences
• Result from regulation at the molecular level

Evidence for Cytoplasmic Signals

• Molecules present in the cytoplasm
• Regulate progress through the cell cycle

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 cell�immediately entered the �S phase—DNA was �synthesized.

S

S

S

M

M

M

G₁

G₁

Experiment 1

Experiment 2

Figure 12.13 A, B

The Cell Cycle Control System

• The sequential events of the cell cycle
• Are directed by a distinct cell cycle control system, which is similar to a clock

Figure 12.14

Control �system

G₂ checkpoint

M checkpoint

G₁ checkpoint

G₁

S

G₂

M

• The clock has specific checkpoints
• Where the cell cycle stops until a go-ahead signal is received

​

G₁ checkpoint

G₁

G₁

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

The Cell Cycle Clock: Cyclins and �Cyclin-Dependent Kinases

• Two types of regulatory proteins are involved in cell cycle control
• Cyclins and cyclin-dependent kinases (Cdks)

• The activity of cyclins and Cdks
• Fluctuates during the cell cycle

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 molecules

combine 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

Cdk

G_2�checkpoint

Cyclin

MPF

Cyclin is �degraded

Degraded�Cyclin

G₁

G₂

S

M

G₁

G₁

S

G₂

G₂

S

M

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

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

3

Figure 12.16 A, B

M

Stop and Go Signs: Internal and External Signals at the Checkpoints

• Both internal and external signals
• Control the cell cycle checkpoints

• Growth factors
• Stimulate other cells to divide

EXPERIMENT

A sample of connective tissue was cut up �into small pieces.

Enzymes were used to digest the extracellular matrix,�resulting in a suspension of free fibroblast cells.

Cells were transferred to sterile culture vessels containing a basic growth medium consisting of glucose, amino acids, salts, and antibiotics (as a precaution against bacterial growth). PDGF was added to half the vessels. The culture vessels were incubated at 37°C.

3

2

1

Petri�plate

Without PDGF

With PDGF

Scalpels

Figure 12.17

• In density-dependent inhibition
• Crowded cells stop dividing
• Most animal cells exhibit anchorage dependence
• In which they must be attached to a substratum to divide

Cells anchor to dish surface and

divide (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 µm

Figure 12.18 A

• Cancer cells
• Exhibit neither density-dependent inhibition nor anchorage dependence

25 µm

Cancer cells do not exhibit�anchorage 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

Loss of Cell Cycle Controls in Cancer Cells

• Cancer cells
• Do not respond normally to the body’s control mechanisms
• Form tumors

• Malignant tumors invade surrounding tissues and can metastasize
• Exporting cancer cells to other parts of the body where they may form secondary tumors

Cancer cells invade �neighboring tissue.

2

A small percentage of �cancer cells may survive �and establish a new tumor �in another part of the body.

4

Cancer cells spread �through lymph and �blood vessels to

other parts of the body.

3

A tumor grows from a �single cancer cell.

1

Tumor

Glandular

tissue

Cancer cell

Blood�vessel

Lymph�vessel

Metastatic�Tumor

Figure 12.19