Chapter 12: Mitosis Cell Division The continuity of life –Is based upon the reproduction of cells,...

Chapter 12: Mitosis

Cell Division

• The continuity of life– Is based upon the reproduction of cells, or cell

division

Figure 12.1

Where it all began…You started as a cell smaller than a period at the end of a sentence…

• Going from egg to baby…. the original fertilized egg has to divide…

and divide…and divide…

and divide…

Getting from there to here…

• For reproduction – asexual reproduction

• one-celled organisms

• For growth– from fertilized egg to

multi-celled organism

• For repair & renewal– replace cells that die

from normal wear & tear or from injury

Why do cells divide?

amoeba

• 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 (46 chromosomes in humans, 23 pairs)

• Body cells

– Gametes • have one set of chromosomes (23 chromosomes in humans)

• Sex cells

Binary Fission

– The bacterial chromosome replicates

– The two daughter chromosomes actively move apart

E. coli cell

OriginOrigin

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

1

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

2

Replication finishes. The plasma membrane grows inward, andnew cell wall is deposited.

3

Two daughter cells result.4

Cell cycle• Cell has a “life cycle”

cell is formed from a mitotic division

cell grows & maturesto divide again

cell grows & matures to never divide again

G1, S, G2, M G1G0

epithelial cells,blood cells,stem cells

liver cells

brain / nerve cellsmuscle cells

• Eukaryotic cell division consists of– Mitosis, the division of the nucleus– Cytokinesis, the division of the cytoplasm

AND…INTERPHASE

G1

S(DNA synthesis)

G2Cyto

kines

is

Mito

sis

MITOTIC(M) PHASE

Figure 12.5

Interphase• 90% of cell life cycle

– cell doing its “everyday job”• synthesize proteins/enzymes, etc

– prepares for duplication if triggered

I ’m working here!

Time to divide& multiply!

• Interphase can be divided into subphases– G1 phase

– S phase

– G2 phase

Interphase• Divided into 3 phases:

– G1 = 1st Gap (Growth)• cell doing its “everyday job”• cell grows

– S = DNA Synthesis• copies chromosomes

– G2 = 2nd Gap (Growth)• prepares for division • cell grows (more)• produces organelles,

proteins, membranes

G0

signal to

divide

double-strandedmitotic humanchromosomes

Mitotic Chromosome

Duplicated chromosome 2 sister chromatids narrow at centromeres contain identical

copies of original DNAhomologouschromosomes

homologouschromosomes

sister chromatidshomologous = “same information”single-stranded

double-stranded

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, which separate during cell division

• The centromere is where the two chromatids are most closely attached

Mitosis • Dividing cell’s DNA between

2 daughter nuclei– “dance of the chromosomes”

• 4 phases– prophase– metaphase– anaphase– telophase

Overview of mitosis

interphase prophase (pro-metaphase)

metaphase anaphase telophase

cytokinesis

I.P.M.A.T.

Prophase Chromatin condenses

– visible chromosomes – chromatids

• Protein fibers cross cell to form mitotic spindle– Made of microtubules/microfilaments – coordinates movement of

chromosomes

• Centrioles move to opposite poles of cell – animal cell only

• Nucleolus disappears• Nuclear membrane breaks down

The Mitotic Spindle• 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

Fig. 12-7

Microtubules Chromosomes

Sisterchromatids

Aster

Metaphaseplate

Centrosome

Kineto-chores

Kinetochoremicrotubules

Overlappingnonkinetochoremicrotubules

Centrosome 1 µm

0.5 µm

Transition to Metaphase • Prometaphase

– spindle fibers attach to centromeres

• creating kinetochores (region where microtubules attach)

• connect centromeres to centrosomes

– chromosomes begin moving

Metaphase • Chromosomes align along

middle of cell– metaphase plate

• meta = middle plane

– spindle fibers coordinate movement

– helps to ensure chromosomes separate properly

• so each new nucleus receives only 1 copy of each chromosome

Anaphase • Sister chromatids separate at

kinetochores – move to opposite poles

– pulled at centromeres

– pulled by motor proteins “walking”along microtubules

• actin, myosin

Fig. 12-8b

Kinetochore

MicrotubuleTubulinSubunits

Chromosome

Chromosomemovement

Motorprotein

CONCLUSION

Telophase• Chromosomes arrive at

opposite poles– daughter nuclei form – nucleoli form– chromosomes disperse

• no longer visible under light microscope

• Spindle fibers disperse• Cytokinesis begins

– cell division

green = key features

Cytokinesis• Animals

– constriction belt of actin microfilaments around equator of cell

• cleavage furrow forms (shallow groove near old metaphase plate)

• splits cell in two• like tightening a draw

string

Mitosis in whitefish blastula

Mitosis in plant cell

Cytokinesis in Plants• Plants

– cell plate forms• vesicles line up at

equator– derived from Golgi

• vesicles fuse to form 2 cell membranes

– new cell wall laid down between membranes

• new cell wall fuses with existing cell wall

Cytokinesis in Animals

(play Cells Alive movies here)

(play Thinkwell movies here)

• 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

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

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

• The cell cycle is regulated by a molecular control system

• Chemical signals in cytoplasm • The frequency of cell division

– Varies with the type of cell (skin vs liver vs brain)

• These cell cycle differences– Result from regulation at the molecular level

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

Control system

G2 checkpoint

M checkpoint

G1 checkpoint

G1

S

G2M

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

received

G1 checkpoint

G1G1

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.

G0 phase: a non-dividing state

• 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

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

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

The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases

• Protein Kinases: enzymes that activate or inactivate other proteins by phosphorylating them

(give go ahead at G1 and G2 checkpoints)

- Cyclins are proteins that cyclically fluctuate concentration

The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases

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

*M phase promoting factor

The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases

• Most of the time kinases in inactive form• Must be attached to a CYCLIN (protein) to be active

• Cyclin-dependent kinases (Cdks)– Activity rises and falls with partner– Ex: MPF triggers the cell’s passage past the G2

checkpoint into M phase– When cyclins are present with MPF, it phosphorylates a

variety of proteins, initiating mitosis

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

Cyclin

accu

mu

latio

n

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

• 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 (extracellular matrix)

Fig. 12-19

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

25 µm

Cancer cells do not exhibitanchorage 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

• 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

• 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

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

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

Fig. 12-20

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

Fig. 12-UN2

Fig. 12-UN5

Mitosis in plant cell