chapter 12 mitosis - ju medicine · 1 nucleus began mitosis without chromosome duplication....

Lecture Presentations by

Nicole Tunbridge and

Kathleen Fitzpatrick

Chapter 12

Mitosis

© 2018 Pearson Education Ltd.

The Key Roles of Cell Division

▪ The ability of organisms to produce more of their

own kind best distinguishes living things from

nonliving matter

▪ The continuity of life is based on the reproduction of

cells, or cell division



Figure 12.1


Figure 12.1a

Chromosomes (blue) are attached byspecific proteins (green) to cell machinery(red) and are moved during division of arat kangaroo cell.

▪ In unicellular organisms, division of one cell

reproduces the entire organism

▪ Multicellular eukaryotes depend on cell division for

▪ development from a fertilized egg

▪ growth

▪ repair

▪ Cell division is an integral part of the cell cycle, the

life of a cell from formation to its own division



Figure 12.2

100 µm (a) Asexual reproduction

(b) Growth anddevelopment

(c) Tissue renewal

50 µm

20 µm

Concept 12.1: Most cell division results in

genetically identical daughter cells

▪ Most cell division results in two daughter cells with

identical genetic information, DNA

▪ The exception is meiosis, a special type of division

that can produce sperm and egg cells


Cellular Organization of the Genetic Material

▪ All the DNA in a cell constitutes the cell’s genome

▪ A genome can consist of a single DNA molecule

(common in prokaryotic cells) or a number of DNA

molecules (common in eukaryotic cells)

▪ DNA molecules in a cell are packaged into

chromosomes



Figure 12.3

20 µm

▪ Eukaryotic chromosomes consist of chromatin, a

complex of DNA and protein that condenses during

cell division

▪ Every eukaryotic species has a characteristic

number of chromosomes in each cell nucleus

▪ Somatic cells (nonreproductive cells) have two sets

of chromosomes

▪ Gametes (reproductive cells: sperm and eggs) have

half as many chromosomes as somatic cells


Distribution of Chromosomes During

Eukaryotic Cell Division

▪ In preparation for cell division, DNA is replicated and

the chromosomes condense

▪ Each duplicated chromosome has two sister

chromatids (joined copies of the original

chromosome), attached along their lengths by

cohesins

▪ The centromere is the narrow “waist” of the

duplicated chromosome, where the two chromatids

are most closely attached



Figure 12.4

Sisterchromatids

Centromeres, one oneach sister chromatid 0.5 µm

▪ During cell division, the two sister chromatids of

each duplicated chromosome separate and move

into two nuclei

▪ Once separate, the chromatids are called

chromosomes



Figure 12.5_1

Chromosomes ChromosomalDNA molecules

Centromere

Chromosomearm

1


Figure 12.5_2


Centromere

Chromosomearm

Chromosome duplication

Sisterchromatids

1

2


Figure 12.5_3


Centromere

Chromosomearm

Chromosome duplication

Sisterchromatids

Separation of sisterchromatids

1

2

3

▪ Eukaryotic cell division consists of

▪ mitosis, the division of the genetic material in 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

half as many chromosomes as the parent cell


Concept 12.2: The mitotic phase alternates with

interphase in the cell cycle

▪ In 1882, the German anatomist Walther Flemming

developed dyes to observe chromosomes during

mitosis and cytokinesis


Phases of the Cell Cycle

▪ The cell cycle consists of

▪ mitotic (M) phase (mitosis and cytokinesis)

▪ interphase (cell growth and copying of chromosomes

in preparation for cell division)


▪ Interphase (about 90% of the cell cycle) can be

divided into three phases:

▪ 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



Figure 12.6

G1

S(DNA synthesis)

G2

▪ Mitosis is conventionally broken down into five

stages:

▪ prophase

▪ prometaphase

▪ metaphase

▪ anaphase

▪ telophase



Figure 12.7a

G2 of Interphase

Centrosomes(with centriolepairs)

Chromosomes(duplicated,uncondensed)

Prophase

Early mitoticspindle

Prometaphase

Nonkinetochoremicrotubules

Fragmentsof nuclearenvelope

Aster

Centromere

NucleolusNuclearenvelope

Plasmamembrane

Two sister chromatidsof one chromosome

Kinetochore Kinetochoremicrotubules

10

µm


Figure 12.7b

Metaphase

Metaphaseplate

Anaphase Telophase and Cytokinesis

Cleavagefurrow

Nucleolusforming

Daughterchromosomes

SpindleCentrosome atone spindle pole

Nuclearenvelopeforming

10

µm


Figure 12.7c

G2 of Interphase

Centrosomes(with centriolepairs)

Chromosomes(duplicated,uncondensed)

Prophase

Early mitoticspindle

Aster

Centromere

NucleolusNuclearenvelope

Plasmamembrane

Two sister chromatidsof one chromosome


Figure 12.7d

Prometaphase

Fragmentsof nuclearenvelope

Nonkinetochoremicrotubules

Metaphase

Metaphaseplate

Kinetochore Kinetochoremicrotubules

Spindle Centrosome atone spindle pole


Figure 12.7e

Anaphase Telophase and Cytokinesis

Cleavagefurrow

Nucleolusforming

Daughterchromosomes

Nuclearenvelopeforming

The Mitotic Spindle: A Closer Look

▪ The mitotic spindle is a structure made of

microtubules that controls chromosome movement

during mitosis

▪ In animal cells, assembly of spindle microtubules

begins in the centrosome, the microtubule-

organizing center

▪ The centrosome replicates during interphase,

forming two centrosomes that migrate to opposite

ends of the cell during prophase and prometaphase


▪ 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

▪ Kinetochores are protein complexes associated

with centromeres

▪ At metaphase, the chromosomes are all lined up at

the metaphase plate, a plane midway between the

spindle’s two poles



Figure 12.8

Sisterchromatids

Aster Centrosome

Metaphaseplate(imaginary)

Kineto-chores

MicrotubulesOverlappingnonkinetochoremicrotubules

Chromosomes

Centrosome

1 µm

Kinetochoremicrotubules

0.5 µm


Figure 12.8a

Microtubules

Chromosomes

Centrosome

1 µm


Figure 12.8b

Kinetochores

Kinetochoremicrotubules

0.5 µm

▪ In anaphase the cohesins are cleaved by an enzyme

called separase

▪ Sister chromatids separate and move along the

kinetochore microtubules toward opposite ends of

the cell

▪ The microtubules shorten by depolymerizing at their

kinetochore ends


▪ Results of a clever experiment suggest that motor

proteins on kinetochores “walk” the chromosomes

along the microtubules during anaphase

▪ The depolymerization of the microtubules at the

kinetochore ends occurs after the motor proteins

have passed

▪ This is called the “Pac-man” mechanism


▪ Nonkinetochore microtubules from opposite poles

overlap and push against each other, elongating the

cell

▪ At the end of anaphase, duplicate groups of

chromosomes have arrived at opposite ends of the

elongated cell

▪ Cytokinesis begins during anaphase or telophase,

and the spindle eventually disassembles


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



Figure 12.10

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

(TEM)

Cleavage furrow 100 µm Wall of parent cell 1 µmVesiclesformingcell plate

New cellwallCell plate

Contractile ring ofmicrofilaments

Daughter cellsDaughter cells


Figure 12.10a

Cleavage furrow 100 µm


Figure 12.10b

Wall of parent cell 1 µmVesiclesformingcell plate


Figure 12.11

Chromosomescondensing

NucleusNucleolus Chromosomes

Prophase Prometaphase

Metaphase Anaphase

10 µ

m

Cell plate

Telophase

1 2

3 4 5


Figure 12.11a

Chromosomescondensing

Nucleus

Nucleolus

Prophase 10 µm1


Figure 12.11b

Chromosomes

Prometaphase 10 µm2


Figure 12.11c

Metaphase 10 µm3


Figure 12.11d

Anaphase 10 µm4


Figure 12.11e

Cell plate

Telophase 10 µm5

Binary Fission in Bacteria

▪ 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

▪ The plasma membrane pinches inward, dividing the

cell into two



Figure 12.12_1

Origin ofreplication

Bacterial cellChromosomereplicationbegins.

Two copiesof origin

Cell wall

Plasmamembrane

Bacterialchromosome

1


Figure 12.12_2



Two copiesof origin

Cell wall

Plasmamembrane

Bacterialchromosome

One copy of theorigin is now ateach end of thecell.

Origin Origin

1

2


Figure 12.12_3



Two copiesof origin

Cell wall

Plasmamembrane

Bacterialchromosome


Replicationfinishes.

Origin Origin

1

2

3


Figure 12.12_4



Two copiesof origin

Cell wall

Plasmamembrane

Bacterialchromosome


Replicationfinishes.

Origin Origin

Two daughtercells result.

1

2

3

4

The Evolution of Mitosis

▪ Because prokaryotes evolved before eukaryotes,

mitosis probably evolved from binary fission

▪ Certain protists exhibit types of cell division that

seem intermediate between binary fission and

mitosis



Figure 12.13

Bacterialchromosome

Kinetochoremicrotubule

Intact nuclearenvelope

(a) Bacteria

Chromosomes

Microtubules

(c) Diatoms and some yeasts

Kinetochoremicrotubule

Intact nuclearenvelope

(b) Dinoflagellates (d) Most eukaryotes

Fragments ofnuclearenvelope

Concept 12.3: The eukaryotic cell cycle is

regulated by a molecular control system

▪ The frequency of cell division varies with the type of

cell

▪ These differences result from regulation at the

molecular level

▪ Cancer cells manage to escape the usual controls

on the cell cycle


The Cell Cycle Control System

▪ 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



Figure 12.14

Experiment Experiment 1 Experiment 2

S

Results

G1 M G1

S S M M

G1 nucleusimmediately enteredS phase and DNAwas synthesized.

Conclusion

G1 nucleus beganmitosis withoutchromosomeduplication.

Molecules present in the cytoplasm controlthe progression to S and M phases.

Data from R. T. Johnson and P. N. Rao, Mammalian cell fusion: Induction of prematurechromosome condensation in interphase nuclei, Nature 226:717–722 (1970).

▪ 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



Figure 12.15

G1 checkpoint

G1

Controlsystem S

M G2

M checkpoint

G2 checkpoint

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 a Cdk rises and falls with changes

in concentration of its cyclin partner

▪ MPF (maturation-promoting factor) is a cyclin-Cdk

complex that triggers a cell’s passage past the G2

checkpoint into the M phase



Figure 12.16a

M G1 S G2 M G1 S G2 M G1

MPF activity

Cyclinconcentration

Time

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


Figure 12.16b

Cdk

Degradedcyclin

Cyclin isdegraded

MPF

G2 Cdkcheckpoint

Cyclin

(b) Molecular mechanisms that help regulate the cell cycle

Stop and Go Signs: Internal and External

Signals at the Checkpoints

▪ Many signals registered at checkpoints come from

cellular surveillance mechanisms within the cell

▪ Checkpoints also register signals from outside

the cell

▪ Three important checkpoints are those in the G1, G2,

and M phases


▪ For many cells, the G1 checkpoint seems to be the

most important

▪ 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



Figure 12.17

G1 checkpoint

G0

G1

G1

M

S

Without go-ahead signal, cellenters G0.

(a) G1 checkpoint

G1

G1

With go-ahead signal, cellcontinues cell cycle.

G1

M G2 M G2

M checkpoint

Anaphase

Prometaphase

Without full chromosome attachment,stop signal is received.

(b) M checkpoint

G2

checkpoint

Metaphase

With full chromosomeattachment, go-ahead signal isreceived.

G2


Figure 12.17a

G1 checkpoint

G0

G1

Without go-ahead signal, cell

enters G0.

(a) G1 checkpoint

G1

With go-ahead signal, cell continues

cell cycle.


Figure 12.17b

G1 G1

M G2 M G2

M checkpoint

G2

checkpoint

Metaphase

With full chromosome attachment,go-ahead signal is received.

Anaphase

Prometaphase

Without full chromosome attachment,stop signal is received.

(b) M checkpoint

▪ An example of an internal signal is that cells will not

begin anaphase until all chromosomes are properly

attached to the spindle at the metaphase plate

▪ This mechanism ensures that daughter cells have

the correct number of chromosomes


▪ External factors that influence cell division include

specific growth factors

▪ Growth factors are released by certain cells and

stimulate other cells to divide

▪ Platelet-derived growth factor (PDGF) is made by

blood cell fragments called platelets

▪ In density-dependent inhibition, crowded cells will

stop dividing



Figure 12.18_1

Scalpels

A sample ofhuman connectivetissue is cutup into smallpieces. Petri

dish

1


Figure 12.18_2

Scalpels


dish

Enzymes digestthe extracellularmatrix, resultingin a suspension offree fibroblasts.

1

2


Figure 12.18_3

Scalpels


dish


Cells are transferredto culture vessels.

1

2

3


Figure 12.18_4

Scalpels


dish


Cells are transferredto culture vessels.

PDGF is addedto half thevessels.

Without PDGF With PDGF Cultured fibroblasts (SEM)

10

µm

1

2

3

4

▪ Most cells also exhibit anchorage dependence—to

divide, they must be attached to a substratum

▪ Density-dependent inhibition and anchorage

dependence check the growth of cells at an optimal

density

▪ Cancer cells exhibit neither type of regulation of their

division



Figure 12.19

Anchorage dependence: cellsrequire a surface for division

Density-dependent inhibition:cells form a single layer

Density-dependent inhibition:cells divide to fill a gap andthen stop

20 µm

(a) Normal mammalian cells

20 µm

(b) Cancer cells


Figure 12.19a

20 µm

(a) Normal mammalian cells


Figure 12.19b

20 µm

(b) Cancer cells

Loss of Cell Cycle Controls in Cancer Cells

▪ Cancer cells do not respond normally to the body’s

control mechanisms

▪ Cancer cells do 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


▪ Cells that acquire the ability to divide indefinitely are

undergoing transformation

▪ Cancer cells that are not eliminated by the immune

system form tumors, masses of abnormal cells within

otherwise normal tissue

▪ If abnormal cells remain only at the original site, the

lump is called a benign tumor


▪ Malignant tumors invade surrounding tissues and

can undergo metastasis, the spread of cancer cells

to other parts of the body, where they may form

additional tumors

▪ Localized tumors may be treated with high-energy

radiation, which damages the DNA in the cancer

cells

▪ To treat metastatic cancers, chemotherapies that

target the cell cycle may be used



Figure 12.20

5 µ

m

Breast cancer cell(colorized SEM)

Tumor

Lymphvessel

Bloodvessel

Cancercell

Cancer cells spreadthrough lymph andblood vessels to otherparts of the body.

Metastatictumor

Glandulartissue

A tumor growsfrom a singlecancer cell.

Cancer cells invadeneighboring tissue.

A small percentageof cancer cells maymetastasize toanother part of thebody.

1 2 3 4

▪ Recent advances in understanding the cell cycle and

cell cycle signaling have led to advances in cancer

treatment

▪ Coupled with the ability to sequence the DNA of cells

in a particular tumor, treatments are becoming more

“personalized”


chapter 12 mitosis - ju medicine · 1 nucleus began mitosis without chromosome duplication....

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