Chapter 10 How Cell Divide Copyright © The McGraw-Hill Companies, Inc. Permission required for...

Chapter 10

How Cell Divide

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Chapters Contents

• Bacteria Cell Division

• Eukaryotic Chromosomes• Overview of the Eukaryotic Cell Cycle• Interphase: Preparation for Mitosis• M Phase: Chromosome Segregation and the

Division of Cytoplasmic Contents• Control of the Cell Cycle

eukaryotes

Section 10.1 Learning Objectives

• Describe process of binary fission– What is final outcome of this process?

3

10.1 Bacterial Cell Division• Bacteria divide by binary fission

– Asexual reproduction– Reproduction is clonal (all cells identical to parent)

• Bacterial genome made up of single, circular chromosome tightly packed in the cell at the nucleoid region.– Prokaryotes do not have nuclei

• New chromosomes are partitioned to opposite ends of the cell– Occurs when the cell elongates (grows)

• Septum forms to divide the cell into 2 cells– Via protein FtsZ

Prior to cell division,the bacterial DNAmolecule replicates.The replication of thedouble-stranded,Circular DNA mole-cule that constitutesthe genome of abacterium begins at aspecific site, calledthe origin of replica-tion (green area).

The replicationenzymes move outin both directionsfrom that site andmake copies of eachstrand in the DNAduplex. The enzymes continue until they meet at another specific site, the terminus of replication (red area).

As the DNA isreplicated, the cellelongates, and theDNA is partitioned in the cell such that the origins are at the ¼ and ¾ positions in the cell and the termini are oriented toward the middle of the cell.

1.

2.

3.

Bacterial cell

Bacterial chromosome:Double-stranded DNA

Origin ofreplication


5.

Septation then begins, in which new membrane and cell wall materialbegin to grow and form a septum at approximately the midpoint of the cell. A protein molecule called FtsZ (orange dots) facilitates this process.

When the septum is complete, the cell pinchesin two, and two daughter cells are formed,each containing a bacterial DNA molecule.

4.

Septum


Septum production

via FtsZ

End result 2 identical

cells

Question 1

Prokaryotic cells divide by —

a. Mitosis

b. Cytokinesis

c. Binary fission

d. Replication

e. Conversion


• Describe the structure of eukaryotic chromosomes.

• Distinguish between homologues and sister chromatids.

• Contrast replicated and nonreplicated chromosomes.

8


Septum

FtsZ protein

Chromosome

ChromosomeMicrotubule

Nucleus

Kinetochore microtubule

Centrioles Kinetochore

Polar microtubule

Spindle pole body


Centriole

Prokaryotes Some Protists Other Protists Animals


Polar microtubule

No nucleus, usually have single circularchromosome. After DNA is replicated, it ispartitioned in the cell.After cell elongation,FtsZ protein assemblesinto a ring and facilitatesseptation and celldivision.

Nucleus present andnuclear enveloperemains intact duringcell division.Chromosomes line up.Microtubule fibers passthrough tunnels in thenuclear membrane andset up an axis forseparation of replicatedchromosomes, and celldivision.

A spindle of micro-tubules forms betweentwo pairs of centrioles atopposite ends of thecell. The spindle passes through one tunnel inthe intact nuclearenvelope. Kinetochoremicrotubules formbetween kinetochoreson the chromosomesand the spindle polesand pull the chromo-somes to each pole.

Nuclear enveloperemains intact; spindlemicrotubules form inside the nucleus between spindle pole bodies. A single kinetochore microtubule attaches to each chromosome andpulls each to a pole.

Spindle microtubulesbegin to form betweencentrioles outside ofnucleus. Centrioles moveto the poles and thenuclear envelope breaksdown. Kinetochoremicrotubules attachkinetochores ofchromosomes to spindlepoles. Polar microtubulesextend toward the centerof the cell and overlap.

Yeasts

Central spindleof microtubules

Fragmentsof nuclearenvelope

DNA Division in Different Organisms

Eukaryotic Chromosomes

• Every species has a different number of chromosomes

• Humans have 46 chromosomes in 23 nearly identical pairs– Additional/missing

chromosomes usually fatal with some exceptions (Chapter 13)

950x


© Biophoto Associates/Photo Researchers, Inc.

Chromosomes Composition• Chromosomes are composed of chromatin –

complex of DNA and protein

• Typical human chromosome 140 million nucleotides long

• In the nondividing nucleus– Heterochromatin – not expressed– Euchromatin – expressed

Heterochromatin vs. Euchromatin

12http://www.histology.leeds.ac.uk/cell/nucleus.php

Chromosome Structure• Nucleosome

– The complex of DNA and histone proteins is termed a nucleosome.

– DNA duplex coiled around 8 histone proteins every 200 nucleotides

– Histones are positively charged and strongly attracted to negatively charged phosphate groups of DNA

DNA Double Helix (duplex) Nucleosome

Histone coreDNA


The double stranded DNA is coiled around a core of eight histones proteins, the complex is termed a nucleosome.

• Nucleosomes wrapped into higher order coils called solenoids– Leads to a fiber 30 nm in diameter– This 30-nm fiber is the usual state of

nondividing (interphase) chromatin

• During mitosis, chromatin in solenoid arranged around scaffold of protein to achieve maximum compaction


Mitotic Chromosome

Chromatin loop

Solenoid

Scaffoldprotein

Scaffold protein

Chromatin LoopRosettes of Chromatin Loops

Levels of Eukaryotic Chromosomal Organization

DNA Double Helix (duplex) Nucleosome

Histone coreDNA


Levels of Eukaryotic Chromosomal Organization

Chromosome Karyotypes• Particular array of chromosomes in an individual

organism is called karyotype.

• Humans are diploid (2n)– 2 complete sets of chromosomes– 46 total chromosomes

• Haploid (n) – 1 set of chromosomes

• Pair of chromosomes are homologous– Each one is a homologue

500x


© CNRI/Photo Researchers, Inc.

A Human Karyotype

Chromosome Replication• Prior to replication, each chromosome

composed of a single DNA molecule

• After replication, each chromosome composed of 2 identical DNA molecules– Held together by cohesin proteins

• Visible as 2 strands held together as chromosome becomes more condensed– One chromosome composed of 2 sister

chromatids


Homologous chromosomes Homologous chromosomes

Cohesinproteins

Kinetochores

Sister chromatids

Sister chromatids

Kinetochore

CentromereCentromere

Replication

Question 3

The unexpressed form of DNA is _____; the expressed form of DNA is ______.

a. Heterochromatin; homochromatin

b. Euchromatin; mesochromatin

c. Mesochromatin; homochromatin

d. heterochromatin; euchromatin

e. None of the above

Question 10

Homologous chromosomes and sister chromatids are the same thing.

a. This is true

b. This is false

Question 9

Where would a researcher find histones?

a. In chromosomes with DNA coiled around them

b. In the spindle apparatus

c. At the formation of the cell plate

d. Surrounding a nuclear pore

e. Bound to a ribosome

Learning Objectives• 10.3 Cell Cycle

– Describe the eukaryotic cell cycle.

• 10.4 Interphase– Describe the events that take place during

interphase.– Illustrate the connection between sister

chromatids after S phase.

25

Eukaryotic Cell Cycle

1. G1 (gap phase 1)– Primary growth phase, longest phase

2. S (synthesis)– Replication of DNA

3. G2 (gap phase 2)– Organelles replicate, microtubules

organize

4. M (mitosis)– Subdivided into 5 phases

5. C (cytokinesis)– Separation of 2 new cells

Interphase

Duration of Cell Cycle• Time it takes to complete a cell cycle varies

greatly

• Mature cells take longer than those embryonic tissue to grow

• Growth occurs during G1, G2, and S phases

• Most variation in length of G1

– Resting phase G0 – cells spend more or less time here

Duration of Cell Cycle• Most variation in the length of the cell cycle

between organisms or cell types occurs in G1

– Cells often pause in G1before DNA replication and enter a resting state called G0

– Resting phase G0 – cells spend more or less time here before resuming cell division.

– Most of cells in animal’s body are in G0 phase– Muscle and nerve cells remain there permanently– Liver cells can resume G1 phase in response to factors

released during injury

M Phase

MetaphaseAnaphase

Telophase

Prometaphase

Prophase

S

G2

G1

Interphase

M Phase

G1

CytokinesisMitosis

SG2

The Cell Cycle

Interphase: Preparation for Mitosis

• G1, S, and G2 phases

– G1 – cells undergo major portion of growth

– S – replicate DNA produce two sister chromatids attached at the centromere

– G2 – chromosomes coil more tightly using motor proteins; centrioles replicate; tubulin synthesis

• Centromere – point of constriction– Kinetochore – attachment site for microtubules– Each sister chromatid has a centromere– Chromatids stay attached at centromere by cohesin


Cohesinproteins

Centromereregion ofchromosome

Kinetochoremicrotubules

Kinetochore

Metaphasechromosome

Sisterchromatids

Kinetochores

Nucleus

Nucleolus

Aster

Centrioles(replicated;animalcells only)

Nuclearmembrane

• DNA has been replicated• Centrioles replicate (animal cells)• Cell prepares for division

Chromatin(replicated)


Interphase G2

Question 4

What happens during the S phase of the cell cycle?

a. Growth and maturation

b. Replication of nuclear DNA

c. Production of extra organelles

d. Separation of chromosomes into sister chromatids

Question 16

Mature neurons can spend the entire animal’s lifetime in —

a. G0

b. G1

c. G2

d. S

e. M


• Describe the phases of mitosis.– PMAT

• Explain the importance of metaphase.

• Compare cytokinesis in plants and animals.

35

M phase: Chromosome Segregation and the Division of

Cytoplasmic Contents

Mitosis is divided into 5 phases:

1. Prophase

2. Prometaphase

3. Metaphase

4. Anaphase

5. Telophase

Prophase

• Individual condensed chromosomes first become visible with the light microscope– Condensation continues throughout prophase

• Spindle apparatus assembles– 2 centrioles move to opposite poles forming spindle

apparatus (no centrioles in plants)– Asters – radial array of microtubules in animals (not

plants)

• Nuclear envelope breaks down

• Chromosomes condense and become visible

• Chromosomes appear as two sister chromatids held together at the centromere

• Cytoskeleton is disassembled: spindle begins to form

• Golgi and ER are dispersed• Nuclear envelope breaks down

Mitotic spindlebeginning to form

Condensedchromosomes

Prophase

Prometaphase• Transition occurs after disassembly of nuclear

envelope• Microtubule attachment

– 2nd group grows from poles and attaches to kinetochores

– Each sister chromatid connected to opposite poles

• Chromosomes begin to move to center of cell – congression – Assembly and disassembly of microtubules– Motor proteins at kinetochores

• Chromosomes attach to microtubules at the kinetochores

• Each chromosome is oriented such that the kinetochores of sister chromatids are attached to microtubules from opposite poles.

• Chromosomes move to equator of the cell

Centromere andkinetochore

Mitoticspindle

Prometaphase

Metaphase

• Alignment of chromosomes along metaphase plate– Not an actual

structure– Future axis of cell

division

Polarmicrotubule

Centrioles

Metaphaseplate

Aster

Kinetochoremicrotubule

Sister chromatids

57µm

© Andrew S. Bajer, University of Oregon

• All chromosomes are aligned at equator of the cell, called the metaphase plate

• Chromosomes are attached to opposite poles and are under tension Polar microtubule

Chromosomesaligned on

metaphase plateKinetochoremicrotubule

Metaphase

Anaphase

• Begins when centromeres split

• Key event is removal of cohesin proteins from all chromosomes

• Sister chromatids pulled to opposite poles

Chromosomes

• Proteins holding centromeres of sister chromatids are degraded, freeing individual chromosomes

• Chromosomes are pulled to opposite poles

• Spindle poles move apart


Polarmicrotubule

Anaphase

Telophase

• Spindle apparatus disassembles

• Nuclear envelope forms around each set of sister chromatids– Now called chromosomes

• Chromosomes begin to uncoil

• Nucleolus reappears in each new nucleus

Polar microtubule

Nucleus reforming

• Chromosomes are clustered at opposite poles and decondense

• Nuclear envelopes re-form around chromosomes

• Golgi complex and ER re-form


Telophase

Cytokinesis

• Cleavage of the cell into equal halves

• Animal cells – constriction of actin filaments produces a cleavage furrow

• Plant cells – cell plate forms between the nuclei

25 µmb.325 µma.a: © David M. Phillips/Visuals Unlimited; b: © Guenter Albrecht-Buehler, Northwestern University, Chicago

Cytokinesis in Animal Cell

Vesicles containingmembrane componentsfusing to form cell plate

Cell wall

19,000×

(top): © E.H. Newcomb & W.P. Wergin/Biological Photo Service

Cytokinesis in Plant Cell

Outcome of Mitosis• After PMAT and cytokinesis

– Two identical daughter cells– Number and types of chromosomes remains

the same• 2n mitosis 2n• n mitosis n

• Used for– Asexual reproduction– Growth– repair

50

Question 13

If a researcher looked at a cell and noticed a straight line of sister chromatids, which phase would they be looking at?

a. Prophase

b. Metaphase

c. Anaphase

d. Telophase

e. Interphase

Question 5

Cytokinesis is the division of the nucleus, and mitosis is the division of the cytoplasm.

a. This is true

b. This is false


• Distinguish the role of checkpoints in the control of the cell cycle

• Characterize the role of the anaphase-promoting complex/cyclosome (APC/C) in mitosis.

• Describe cancer in terms of cell cycle control.– Proto-oncogenes & tumor suppressor genes

53

Control of the Cell Cycle

Current view integrates 2 concepts

1.Cell cycle has two irreversible points– Replication of genetic material– Separation of the sister chromatids

2.Cell cycle can be put on hold at specific points called checkpoints

– Process is checked for accuracy and can be halted if there are errors

– Allows cell to respond to internal and external signals

3 Checkpoints1. G1/S checkpoint

– Cell “decides” whether or not to divide– Primary point for external signal influence

2. G2/M checkpoint

– Cell makes a commitment to mitosis– Assesses success of DNA replication– Can stall the cycle if DNA has not been

accurately replicated.

3. Late metaphase (spindle) checkpoint– Cell ensures that all chromosomes are

attached to the spindle

G2

M

S

G2/M checkpoint Spindle checkpoint

G1/S checkpoint(Start or restriction point) G1

3 Checkpoints

Cyclin-dependent kinases (Cdks)

• Enzyme kinases that phosphorylate proteins• Primary mechanism of cell cycle control• Cdks partner with different cyclins at different

points in the cell cycle• For many years, a common view was that

cyclins drove the cell cycle – that is, the periodic synthesis and destruction of cyclins acted as a clock

• Now clear that Cdk itself is also controlled by phosphorylation

G2/M Checkpoint

Cdc2/Mitotic Cyclin

• DNA integrity

• Replication completed

Spindle Checkpoint

APC

• Chromosomes attached at metaphase plate

M

G2

G1S

G1/S Checkpoint

• Size of cell

• Nutritional state of cell

• Growth factors

Cdc2/G1 Cyclin

Checkpoints of the Yeast Cell Cycle

• Cdk – cyclin complex– Also called mitosis-promoting factor (MPF)

• Activity of Cdk is also controlled by the pattern of phosphorylation– Phosphorylation at one site (red) inactivates Cdk– Phosphorylation at another site (green) activates Cdk

Cyclin-dependent kinase(Cdk)

Cyclin

P

P

The Action of MPF

• Once thought that MPF was controlled solely by the level of the M phase-specific cyclins

• Although M phase cyclin is necessary for MPF function, activity is controlled by inhibitory phosphorylation of the kinase component, Cdc2

• Damage to DNA acts through a complex pathway to tip the balance toward the inhibitory phosphorylation of MPF

Anaphase-promoting complex (APC)

• Also called cyclosome (APC/C)

• At the spindle checkpoint, presence of all chromosomes at the metaphase plate and the tension on the microtubules between opposite poles are both important

• Function of the APC/C is to trigger anaphase itself

• Marks securin for destruction; no inhibition of separase; separase destroys cohesin

G2/M Checkpoint

Cdk1/Cyclin B

• DNA integrity

• Replication completed

Spindle Checkpoint

APC

• Chromosomes attached at metaphase plate

M

G2

G1S

G1/S Checkpoint

• Size of cell

• Nutritional state of cell

• Growth factors

Cdk2/Cyclin E

Checkpoints of the Mammalian Cell Cycle

Cancer

Unrestrained, uncontrolled growth of cells

•Failure of cell cycle control

•Two kinds of genes can disturb the cell cycle when they are mutated

1. Tumor-suppressor genes

2. Proto-oncogenes

Tumor-suppressor genes

• p53 plays a key role in G1 checkpoint

• p53 protein monitors integrity of DNA

• Prevent the development of mutated cells containing mutations

• p53 is absent or damaged in many cancerous cells

1. DNA damage is caused by heat, radiation, or chemicals.

2. Cell division stops, and p53 triggers enzymes to repair damaged region.

3. p53 triggers the destruction of cells damaged beyond repair.

p53 allows cells withrepaired DNA to divide.

1. DNA damage is caused by heat, radiation, or chemicals.

2. The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA.

3. Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous.

DNA repair enzyme

Cancer cell

p53protein

p53protein

No

rma

l p

53

A

bn

orm

al

p5

3

Abnormalp53 protein Abnormal

p53 protein

• Normal p53 protein destroys cells that have irreparable damage to their DNA

• Abnormal p53 protein fails to stop cell division, damaged cells divide, cancer develops

Proto-oncogenes

• Proto-oncogenes are normal cellular genes that become oncogenes when mutated

• Some encode receptors for growth factors–If receptor is mutated in “on,” cell no longer depends on growth factors

• Only one copy of a proto-oncogene needs to undergo this mutation for uncontrolled division to take place

Tumor-suppressor genes

• p53 gene and many others

• Both copies of a tumor-suppressor gene must lose function for the cancerous phenotype to develop

• First tumor-suppressor identified was the retinoblastoma susceptibility gene (Rb)

Proto-oncogenes

Growth factor receptor: more per cell in many breast cancers.

Ras protein: activated by mutations in 20–30% of all cancers.

Src kinase: activated by mutations in 2–5% of all cancers.

Tumor-suppressor Genes

Rb protein: mutated in 40% of all cancers.

p53 protein: mutated in 50% of all cancers.

Cell cyclecheckpoints

Rasprotein

Rbprotein p53

protein

Srckinase

Mammalian cell

NucleusNucleus

Cytoplasm

Key Proteins Associated with Human Cancers

Question 11

Injecting MPF (maturation promoting factor) into cells —

a. Signals apoptosis

b. Causes cell lysis

c. Induces mitosis

d. Moves the cell into G0

e. Inactivates the p53 gene

Question 17

If a cell’s proto-oncogenes are mutated and over expressed, which of the following is most likely to happen?

a. The cell will grow faster

b. The cell will not finish the cell cycle

c. The cell will improperly replicate DNA

d. The cell will prematurely move to G0

e. The cell will undergo binary fission

Question 14

50% of cancerous cells have nonfunctioning p53 proteins. How does p53 help prevent cells from becoming cancerous?

a. It binds growth factors

b. It checks DNA for damage

c. It induces the shift from G1 to S

d. It stops mutations from occurring

e. None of the above

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