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10/18/2011 1 Chapter 12 – Cell Cycle - Mitosis Outline I. Overview II. Mitotic Phase I. Prophase II. Prometaphase III. Metaphase IV. Telophase V. Cytokinesis III. Binary fission IV. Cell Cycle Control Overview: 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 © 2011 Pearson Education, Inc. Figure 12.1 In unicellular organisms, division of one cell reproduces the entire organism Multicellular organisms depend on cell division for Development from a fertilized cell Growth Repair Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division © 2011 Pearson Education, Inc. Overview: The Key Roles of Cell Division Most cell division results in genetically identical daughter cells Most cell division results in daughter cells with identical genetic information, DNA The exception is meiosis, a special type of division that can produce sperm and egg cells (next weeks lab) © 2011 Pearson Education, Inc.

NVC Biol 120 12 Mitosis - Napa Valley College 120 Lectures/NVC... · Right-click slide / select ”Play ... 1 Prophase 2 Prometaphase 3 Metaphase 4 Anaphase 5 Telophase Figure 12.11a

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10/18/2011

1

Chapter 12 – Cell Cycle - Mitosis Outline

I. OverviewII. Mitotic Phase

I. ProphaseII. PrometaphaseIII. MetaphaseIV. TelophaseV. Cytokinesis

III. Binary fissionIV. Cell Cycle Control

Overview: 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

© 2011 Pearson Education, Inc.

Figure 12.1

In unicellular organisms, division of one cell reproduces the entire organism

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

Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division

© 2011 Pearson Education, Inc.

Overview: The Key Roles of Cell Division Most cell division results in genetically identical daughter cells

Most cell division results in daughter cells with identical genetic information, DNA

The exception is meiosis, a special type of division that can produce sperm and egg cells (next weeks lab)

© 2011 Pearson Education, Inc.

10/18/2011

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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

© 2011 Pearson Education, Inc.

Figure 12.3

20 m

Chromosomes

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

© 2011 Pearson Education, Inc.

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), which separate during cell division

The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached

© 2011 Pearson Education, Inc.

Figure 12.4

0.5 mCentromere

Sisterchromatids

During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei

Once separate, the chromatids are called chromosomes

© 2011 Pearson Education, Inc.

Distribution of Chromosomes During Eukaryotic Cell Division

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Figure 12.5-1

ChromosomesChromosomalDNA molecules

Centromere

Chromosomearm

1

Figure 12.5-2

ChromosomesChromosomalDNA molecules

Centromere

Chromosomearm

Chromosome duplication(including DNA replication)and condensation

Sisterchromatids

1

2

Figure 12.5-3

ChromosomesChromosomalDNA molecules

Centromere

Chromosomearm

Chromosome duplication(including DNA replication)and condensation

Sisterchromatids

Separation of sisterchromatids intotwo chromosomes

1

2

3

The region where the chromatids are tightly associated is called

1 2 3 4

25% 25%25%25%1. Centrosome2. Chromatin3. Centromere4. Kinetochore

Microtubule-organizing centers have two

1 2 3 4

25% 25%25%25%1. Centrioles2. Chromatins3. Centromeres4. Kinetochores

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 only one set of chromosomes, half as many as the parent cell

© 2011 Pearson Education, Inc.

Eukaryotic Cell Division

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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

© 2011 Pearson Education, Inc.

When does DNA replicate?

Just prior to cell division

Cells need to divide for organisms to grow or to replace old cells, or for one celled organisms to reproduce

Before a cell divides it needs to replicate its DNA

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)

© 2011 Pearson Education, Inc.

Interphase (about 90% of the cell cycle) 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

© 2011 Pearson Education, Inc.

Phases of the Cell Cycle - Interphase

Figure 12.6

INTERPHASE

G1

G2

S(DNA synthesis)

Mitotic Phase

Mitosis is conventionally divided into five phases Prophase Prometaphase Metaphase Anaphase Telophase

Cytokinesis overlaps the latter stages of mitosis

© 2011 Pearson Education, Inc.

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© 2011 Pearson Education, Inc. BioFlix: Mitosis

Figure 12.7

G2 of Interphase Prophase PrometaphaseCentrosomes(with centriole pairs)

Chromatin(duplicated)

Nucleolus Nuclearenv elope

Plasmamembrane

Early mitoticspindle

AsterCentromere

Chromosome, consistingof two sister chromatids

Fragments of nuclearenv elope

Nonkinetochoremicrotubules

Kinetochore Kinetochoremicrotubule

Metaphase

Metaphase plate

Anaphase Telophase and Cytokinesis

Spindle Centrosome atone spindle pole

Daughterchromosomes

Cleav agefurrow

Nucleolusforming

Nuclearenv elopeforming

10

m

Figure 12.7a

G2 of Interphase Prophase Prometaphase

Centrosomes(with centriole pairs)

Chromatin(duplicated)

NucleolusNuclearenvelope

Plasmamembrane

Early mitoticspindle

AsterCentromere

Chromosome, consistingof two sister chromatids

Fragments of nuclearenvelope

Nonkinetochoremicrotubules

Kinetochore Kinetochoremicrotubule

Figure 12.7b

Metaphase

Metaphase plate

Anaphase Telophase and Cytokinesis

Spindle Centrosome atone spindle pole

Daughterchromosomes

Cleavagefurrow

Nucleolusforming

Nuclearenvelopeforming

Figure 12.7c

G2 of Interphase Prophase Prometaphase

10

m

Figure 12.7d

10

m

Metaphase Anaphase Telophase and Cytokinesis

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G2 of Interphase Prophase Prometaphase

Centrosomes(with centriole pairs)

Chromatin(duplicated)

NucleolusNuclearenvelope

Plasmamembrane

G2 of Interphase

Nuclear envelope present Centrosomes are duplicated Chromosomes are in the

duplicated state (DNA replication occurred during S phase of interphase)

Prophase

Early mitoticspindle

AsterCentromere

Chromosome, consistingof two sister chromatids

Prophase

Chromosomes condense Nucleolus disappear Sister chromatids are joined

at the centromeres Mitotic spindle appears,

composed of centrosomes, spindle microtubles and asters

Centrosomes move to opposite poles of the cell

PrometaphaseFragments of nuclearenvelope

Nonkinetochoremicrotubules

Kinetochore Kinetochoremicrotubule

Prometaphase

Nuclear envelope fragments

Microtubles attach to the kinetochore

Metaphase

Metaphase plate

Telophase and Cytokinesis

Spindle Centrosome atone spindle pole

Metaphase

Centrosomes are at opposite ends of cell

Chromosomes line up at the metaphase plate

Anaphase

Daughterchromosomes

Metaphase Cohesion proteins are cleaved,

sister chromatids separate, now each are a chromosome

Kinetochore microtubules shorten, moving the daughter chromosomes to opposite poles of the cell

Cell elongates due to nonkinetochore microtubules lengthening

Telophase and Cytokinesis

Cleavagefurrow

Nucleolusforming

Nuclearenvelopeforming

Telophase

Two identical daughter nuclei form, nuclear envelopes form

Nucleolus reappears Chromosomes uncondense Spindle microtubles

depolymerize

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Telophase and Cytokinesis

Cleavagefurrow

Nucleolusforming

Nuclearenvelopeforming

Cytokinesis

Cytoplasm divides In animal cells, cleavage

furrow pinches the cell in two

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

© 2011 Pearson Education, Inc.

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

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

© 2011 Pearson Education, Inc.

The Mitotic Spindle: A Closer Look

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, an imaginary structure at the midway point between the spindle’s two poles

© 2011 Pearson Education, Inc.

The Mitotic Spindle: A Closer Look

Figure 12.8

Sisterchromatids

AsterCentrosome

Metaphaseplate(imaginary)

Kineto-chores

Overlappingnonkinetochoremicrotubules Kinetochore

microtubules

Microtubules

Chromosomes

Centrosome

0.5 m

1 m

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

© 2011 Pearson Education, Inc.

The Mitotic Spindle: A Closer Look

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Figure 12.9

Chromosomemovement

Microtubule

Motor protein

Chromosome

Kinetochore

Tubulinsubunits

Kinetochore

Mark

Spindlepole

EXPERIMENT

RESULTS

CONCLUSION

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 begins during anaphase or telophase and the spindle eventually disassembles

© 2011 Pearson Education, Inc.

The Mitotic Spindle: A Closer Look

The place where microtubules attach is called the

1 2 3 4

25% 25%25%25%1. Centriole2. Chromatin3. Centromere4. Kinetochore

Where does DNA replication take place?

1 2

50%50%1. Cytosol2. Nucleus

During this stage the nuclear membrane breaks down

1 2 3 4

25% 25%25%25%1. Metaphase2. Anaphase3. Prophase4. Telophase

During this stage chromosomes line up at the equator

1 2 3 4

25% 25%25%25%1. Metaphase2. Anaphase3. Prophase4. Telophase

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During this stage the chromosomes begin to uncondense

1 2 3 4

25% 25%25%25%1. Metaphase2. Anaphase3. Prophase4. Telophase

At the end of Mitosis the chromosomes are in the duplicated state

1 2

50%50%1. Yes2. No

© 2011 Pearson Education, Inc.

Animation: Cytokinesis Right-click slide / select ”Play”

© 2011 Pearson Education, Inc.

Animation: Animal Mitosis Right-click slide / select ”Play”

© 2011 Pearson Education, Inc.

Animation: Sea Urchin (Time Lapse) Right-click slide / select ”Play”

Videos

Youtube Mitosis in embryo Mitosis

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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

© 2011 Pearson Education, Inc.

Figure 12.10

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

Cleavage furrow

Contractile ring ofmicrofilaments

Daughter cells

Vesiclesformingcell plate

Wall of parent cell

Cell plate New cell wall

Daughter cells

100 m1 m

Figure 12.10a (a) Cleavage of an animal cell (SEM)

Cleavage furrow

Contractile ring ofmicrofilaments

Daughter cells

100 m

Figure 12.10b (b) Cell plate formation in a plant cell (TEM)

Vesiclesformingcell plate

Wall of parent cell

Cell plate New cell wall

Daughter cells

1 m

Figure 12.10c

Cleavage furrow

100 m

Figure 12.10d

Vesiclesformingcell plate

Wall of parent cell 1 m

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Figure 12.11

ChromatincondensingNucleus

Nucleolus Chromosomes Cell plate10 m

Prophase Prometaphase Metaphase Anaphase Telophase1 2 3 4 5

Figure 12.11a

ChromatincondensingNucleus

Nucleolus

Prophase1

10 m

Figure 12.11b

Chromosomes

Prometaphase2

10 m

Figure 12.11c

10 m

Metaphase3

Figure 12.11d

Anaphase4

10 m

Figure 12.11e

10 m

Telophase5

Cell plate

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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

© 2011 Pearson Education, Inc.

Figure 12.12-1

1

Origin ofreplication

E. coli cell

Two copies of origin

Cell wallPlasma membrane

Bacterial chromosomeChromosomereplicationbegins.

1

Origin ofreplication

E. coli cell

Two copies of origin

Cell wallPlasma membrane

Bacterial chromosome

Origin Origin

Chromosomereplicationbegins.

Replicationcontinues.

2

Figure 12.12-2

1

Origin ofreplication

E. coli cell

Two copies of origin

Cell wallPlasma membrane

Bacterial chromosome

Origin Origin

Chromosomereplicationbegins.

Replicationcontinues.

Replicationfinishes.

2

3

Figure 12.12-3

1

Origin ofreplication

E. coli cell

Two copies of origin

Cell wallPlasma membrane

Bacterial chromosome

Origin Origin

Chromosomereplicationbegins.

Replicationcontinues.

Replicationfinishes.

Two daughtercells result.

2

3

4

Figure 12.12-4

The Evolution of Mitosis

Since 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

© 2011 Pearson Education, Inc.

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Figure 12.13

(a) Bacteria

(b) Dinoflagellates

(d) Most eukaryotes

Intact nuclearenvelope

Chromosomes

Microtubules

Intact nuclearenvelope

Kinetochoremicrotubule

Kinetochoremicrotubule

Fragments ofnuclear envelope

Bacterialchromosome

(c) Diatoms andsome yeasts

At the end of Mitosis the chromosomes are in the duplicated state

1 2

50%50%1. Yes2. No

At the end of mitosis in plants the cell wall forms by

1 2 3

33% 33%33%1. Proteins constrict and pinch off the new cell

2. Vesicles line up between the cells and join together

3. The new cell wall grows out from old cell wall

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

© 2011 Pearson Education, Inc.

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

© 2011 Pearson Education, Inc.

G1 checkpoint

G1

G2

G2 checkpointM checkpoint

M

SControlsystem

Figure 12.15

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

If a cell receives a go-ahead signal at the G1checkpoint, 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

© 2011 Pearson Education, Inc.

The Cell Cycle Control System Figure 12.16

G1 checkpoint

G1 G1

G0

(a) Cell receives a go-aheadsignal.

(b) Cell does not receive ago-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)

Cdks activity fluctuates during the cell cycle because it is controled by cyclins, so named because their concentrations vary with 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

© 2011 Pearson Education, Inc.

Figure 12.17

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

(b) Molecular mechanisms that help regulate the cell cycle

MPF activityCyclinconcentration

Time

M M MS SG1 G2 G1 G2 G1

Cdk

Degradedcyclin

Cyclin isdegraded

MPF

G2checkpoint Cdk

Cyclin

Figure 12.17a

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

MPF activityCyclinconcentration

Time

M M MS SG1 G2 G1 G2 G1

(b) Molecular mechanisms that help regulate the cell cycle

Cdk

Degradedcyclin

Cyclin isdegraded

MPF

G2checkpoint Cdk

Cyclin

Figure 12.17b

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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

© 2011 Pearson Education, Inc.

Cancer Genes

Cancer is often caused by mutations in two types of genes: Proto-Oncogenes

Tumor-Suppressor Genes

24-5

Proto-Oncogenes

Proto-Oncogenes – Part of the DNA that codes for “gas pedal” proteins.

When proto-oncogenes mutate they become cancer-causing genes called oncogenes.

Example of a proto-oncogene = ras gene The ras protein is a G protein that relays a signal from

a growth factor receptor to a cascade of protein kinases, the end result of the cascade is a the synthesis of a protein that stimulates the cell cycle

24-5

Tumor-Suppressor Genes

Tumor-Suppressor Genes – Part of the DNA that codes for the “brake” proteins. Usually recessive

When tumor-suppressor genes mutate their products no longer inhibit the cell cycle nor promote apoptosis.

An example is the p53 gene. This gene codes for a transcription factor that promotes the synthesis of cell cycle-inhibiting proteins. p53 transcription factor promotes the p21 gene, a cell

cycle inhibitor p53 also activates apoptosis genes

24-5

Causes of Cancer - Heredity BRCA1 and BRCA2—mutated tumor

suppressor genes that may cause breast and ovarian cancer.

RB gene—mutated tumor suppressor gene that may cause retinoblastoma tumor.

RET gene—proto-oncogene which predisposes one to thyroid cancer.

24-8

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Figure 12.18

A sample of humanconnective tissue iscut up into smallpieces.

Enzymes digestthe extracellularmatrix, resulting ina suspension offree fibroblasts.

Cells are transferred toculture vessels.

Scalpels

Petridish

PDGF is addedto half thevessels.

Without PDGF With PDGF

10 m

1

2

34

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

A clear 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

Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence

© 2011 Pearson Education, Inc.

Figure 12.19

Anchorage dependence

Density-dependent inhibition

Density-dependent inhibition

(a) Normal mammalian cells (b) Cancer cells20 m 20 m

Loss of Cell Cycle Controls in Cancer Cells

Cancer cells do not respond normally to the body’s control mechanisms

Cancer 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

© 2011 Pearson Education, Inc.

A normal cell is converted to a cancerous cell by a process called 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 metastasize, exporting cancer cells to other parts of the body, where they may form additional tumors

© 2011 Pearson Education, Inc.

Loss of Cell Cycle Controls in Cancer CellsFigure 12.20

Glandulartissue

Tumor

Lymph vesselBloodvessel

Cancercell

Metastatictumor

A tumor growsfrom a singlecancer cell.

Cancer cells invade neighboringtissue.

Cancer cells spreadthrough lymph andblood vessels to other parts of the body.

Cancer cells may survive and establisha new tumor in another part of the body.

4321

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Figure 12.UN05 Important concepts

Know all the vocabulary presented in the lecture

Know the form (condensed vs uncondensed) that DNA is in during cell division vs interphase

Know the roles of microtubules, and their structure

Know the role of microtubule-organizing centers Know the two stages of cell cycle (interphase

and mitotic phase

Important concepts

Know what happens during the stages of interphase: G1 phase, S phase, G2 phase.

Know what happens during each checkpoint

Know the role of microfilaments in cell division of animal cells, the structure of microfilaments

Important concepts

Understand how cytokinesis takes place in animal and plant cells

Know the basics of cell division in prokaryotic cells

Understand the controls on cell cycle including the role of cdks and cyclin, MFP, tumor suppressor genes and proto-oncogenes

Important Concepts for Lab Exam

For Mitosis: Know each stage, the order of the stages, and what happens in each stage.

Know what the end result is of mitosis Know what state the cell and the

chromosomes are in at the beginning and end of mitosis. For example: Are the cells haploid or diploid? Are the chromosomes duplicated, or not duplicated? How many chromosomes are there in the cell? Are they in pairs?

Be able to identify the stages using models and slides