Chapter 12

The Cell Cycle

Overview: The Key Roles of Cell Division

The ability of organisms to reproduce their own kind is the one characteristic that best distinguishes living things from nonliving matter.

Figure 12.1

The continuity of life is based on the reproduction of cells, or cell division.

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 cellGrowthRepair

20 µm200 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

Concept 12.1: Cell division results in genetically identical daughter cells

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

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 MaterialA cell’s endowment of DNA, its genetic

information Is called its genome

In prokaryotes, the genome is often a single long DNA molecule.

In eukaryotes, the genome consists of several DNA molecules.

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 Later in cell division, the sister chromatids

separate After the sister chromatids separate, they are

considered individual chromosomes. Each new nucleus receives a group of

chromosomes identical to the original group in the parent cell.

Fig. 12-40.5 µm Chromosomes

Chromosomeduplication(including DNAsynthesis)

Chromo-some arm

Centromere

Sisterchromatids

DNA molecules

Separation ofsister chromatids

Centromere

Sister chromatids

Eukaryotic cell division...

Eukaryotic cell division consists of: Mitosis, the division of the nucleus Cytokinesis, the division of the cytoplasm

Gametes are produced by a variation of cell division called meiosis

Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell

Concept 12.2: The mitotic phase alternates with interphase in the cell cycle

The mitotic (M) phase of the cell cycle, which includes mitosis and cytokinesis, alternates with the much longer interphase. Interphase accounts for about 90% of the cell

cycle.

Phases of the Cell Cycle

The cell cycle consists of The mitotic phase Interphase INTERPHASE

G1

S(DNA synthesis)

G2Cyto

kines

is

Mito

sis

MITOTIC(M) PHASE

Figure 12.5

Phases of the cell cycle

Interphase can be divided into subphases G1 phase (“first gap”) S phase (“synthesis”) G2 phase (“second gap”)

The cell grows during all three phases, but chromosomes are duplicated only during the S phase

The mitotic phase (M) Is made up of mitosis and cytokinesis

Mitosis is conventionally divided into five phases:

Prophase Prometaphase Metaphase Anaphase Telophase

Cytokinesis is well underway by late telophase

BioFlix: MitosisBioFlix: Mitosis

Mitosis is a continuum of changesProphasePrometaphase

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 Figure 12.6

Nonkinetochoremicrotubules

Mitosis consists of five distinct phasesMetaphaseAnaphaseTelophase

Centrosome at one spindle pole

Daughter chromosomes

METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS

Spindle

Metaphaseplate Nucleolus

forming

Cleavagefurrow

Nuclear envelopeforming

Figure 12.6

The Mitotic Spindle: A Closer Look

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

During prophase, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center

The centrosome replicates, forming two centrosomes that migrate to opposite ends of the cell, as spindle microtubules grow out from them

An aster (a radial array of short microtubules) extends from each centrosome

The spindle includes the centrosomes, the spindle microtubules, and the asters

During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes

At metaphase, the chromosomes are all lined up at the metaphase plate, the midway point between the spindle’s two poles

Fig. 12-7

Microtubules Chromosomes

Sisterchromatids

Aster

Metaphaseplate

Centrosome

Kineto-chores

Kinetochoremicrotubules

Overlappingnonkinetochoremicrotubules

Centrosome 1 µm

0.5 µm

Video: Animal MitosisVideo: Animal Mitosis

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

The microtubules shorten by depolymerizing at their kinetochore ends

Fig. 12-8

EXPERIMENT

Kinetochore

RESULTS

CONCLUSION

Spindlepole

Mark

Chromosomemovement

Kinetochore

MicrotubuleMotorprotein

Chromosome

Tubulinsubunits

Nonkinetechore microtubules...

Nonkinetochore 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

In plant cells, a cell plate forms during cytokinesis

Animation: CytokinesisAnimation: Cytokinesis

Video: Sea Urchin (Time Lapse)Video: Sea Urchin (Time Lapse)

Fig. 12-9

Cleavage furrow100 µm

Contractile ring ofmicrofilaments

Daughter cells

(a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM)

Vesiclesformingcell plate

Wall ofparent cell

Cell plate

Daughter cells

New cell wall

1 µm

Mitosis in a plant cell

1 Prophase. The chromatinis 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 discretechromosomes; each consists of two identical sister chromatids. Laterin prometaphase, the nuclear envelop will fragment.

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

Anaphase. Thechromatids of each chromosome have separated, and the daughter chromosomesare moving to the ends of cell as their kinetochoremicrotubles shorten.

Telophase. Daughternuclei are forming. Meanwhile, cytokinesishas started: The cellplate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell.

2 3 4 5

NucleusNucleolus

ChromosomeChromatinecondensing

Figure 12.10

Binary Fission

Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission

In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart

Fig. 12-11-4

Origin ofreplication

Two copiesof origin

E. coli cellBacterialchromosome

Plasmamembrane

Cell wall

Origin Origin

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

Fig. 12-12ab

Bacterialchromosome

Chromosomes

Microtubules

(a) Bacteria

(b) Dinoflagellates

Intact nuclearenvelope

Fig. 12-12cd

Kinetochoremicrotubule

(c) Diatoms and yeasts

Kinetochoremicrotubule

(d) Most eukaryotes

Fragments of nuclear envelope

Intact nuclearenvelope

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

The cell cycle appears to be driven by specific chemical signals present in the cytoplasm

Some evidence for this hypothesis comes from experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei

Fig. 12-13

Experiment 1 Experiment 2

EXPERIMENT

RESULTS

S G1M G1

M MSS

When a cell in theS phase was fused with a cell in G1, the G1 nucleus immediatelyentered the Sphase—DNA was synthesized.

When a cell in theM phase was fused with a cell in G1, the G1 nucleus immediatelybegan mitosis—aspindle formed andchromatin condensed,even though thechromosome had notbeen duplicated.

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

The cell cycle control system is regulated by both internal and external controls

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

Fig. 12-14

SG1

M checkpoint

G2M

Controlsystem

G1 checkpoint

G2 checkpoint

For many cells, the G1 checkpoint seems to be the most important one

If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide

If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase

Fig. 12-15

G1

G0

G1 checkpoint

(a) Cell receives a go-ahead signal

G1

(b) Cell does not receive a go-ahead signal

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

MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G2 checkpoint into the M phase

Fig. 12-17

M G1S G2

M G1S G2

M G1

MPF activity

Cyclinconcentration

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

Degradedcyclin

Cdk

G 1S

G 2

M

CdkG2

checkpointCyclin isdegraded

CyclinMPF

(b) Molecular mechanisms that help regulate the cell cycle

Cy

clin

ac

cu

mu

latio

n

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

An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase

Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide

For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture

Fig. 12-18

Petriplate

Scalpels

Cultured fibroblasts

Without PDGFcells fail to divide

With PDGFcells prolifer-ate

10 µm

Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing

Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide

Anchorage dependence

Density-dependent inhibition

Density-dependent inhibition

(a) Normal mammalian cells (b) Cancer cells25 µm25 µm

Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence

Loss of Cell Cycle Controls in Cancer CellsCancer cells do not respond normally to

the body’s control mechanismsCancer cells may not need growth factors

to grow and divide: They may make their own growth factor They may convey a growth factor’s signal

without the presence of the growth factor They may have an abnormal cell cycle control

system

A normal cell is converted to a cancerous cell by a process called transformation

Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue

If abnormal cells remain at the original site, the lump is called a benign tumor

Tumor

A tumor growsfrom a singlecancer cell.

Glandulartissue

Lymphvessel

Bloodvessel

Metastatictumor

Cancercell

Cancer cellsinvade neigh-boring tissue.

Cancer cells spreadto other parts ofthe body.

Cancer cells maysurvive andestablish a newtumor in anotherpart of the body.

1 2 3 4

Malignant tumors invade surrounding tissues and can metastasizeExporting cancer cells to other parts of the

body where they may form secondary tumors

Cancer Treatments

High-energy radiation and chemotherapy with toxic drugs These treatments target actively dividing cells. Chemotherapeutic drugs interfere with specific

steps in the cell cycle. For example, Taxol prevents microtubule

depolymerization, preventing cells from proceeding past metaphase.

The side effects of chemotherapy are due to the drug’s effects on normal cells.

Fig. 12-UN3

Fig. 12-UN4

Fig. 12-UN5

You should now be able to:

1. Describe the structural organization of the prokaryotic genome and the eukaryotic genome

2. List the phases of the cell cycle; describe the sequence of events during each phase

3. List the phases of mitosis and describe the events characteristic of each phase

4. Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

5. Compare cytokinesis in animals and plants

6. Describe the process of binary fission in bacteria and explain how eukaryotic mitosis may have evolved from binary fission

7. Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls

8. Distinguish between benign, malignant, and metastatic tumors

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings