Cap 12 - Ciclo Celular

LECTURE PRESENTATIONSFor CAMPBELL BIOLOGY, NINTH EDITION

Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson

© 2011 Pearson Education, Inc.

Lectures byErin Barley

Kathleen Fitzpatrick

The Cell Cycle

Chapter 12

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

• “Every cell from a cell” (Virchow, 1855).


Figure 12.1 How do a cell’s chromosomes change during cell division?

• 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


(a) Reproduction

(b) Growth and development

(c) Tissue renewal20 m

100 m

200 m

Figure 12.2 The functions of cell division.

Concept 12.1: 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


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


20 m

Figure 12.3 Eukaryotic 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


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


Figure 12.4 A highly condensed, duplicated human chromosome (SEM).

0.5 m Centromere

Sister chromatids

Cohesins

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

• Once separate, the chromatids are called chromosomes


ChromosomesChromosomal

DNA molecules

Centromere

Chromosomearm

Chromosome duplication(including DNA replication)and condensation

Sisterchromatids

Separation of sisterchromatids intotwo chromosomes

1

2

3

Figure 12.5 Chromosome duplication and distribution during cell division.

• 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


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

• Walther Flemming, the German anatomist, was responsible for the discovery of mitosis and cytokinesis, which refers to cell division.– He used aniline dyes to isolate from the gills and fins of salamanders a substance that he called "chromatin”

• In 1882, his results on the stages of mitosis were published in a book entitled, "Cell Substance, Nucleus and Cell Division”

• Based on his research, Flemming concluded that each cell's nuclei comes from another cell nucleus.



Phases of the Cell Cycle

INTERPHASE

G1

G2

S(DNA synthesis)

MITOTIC (M) PHASE

Cytokinesis

Mito

sis

• The cell cycle consists of:–Mitotic (M) phase -mitosis and cytokinesis

• Mitosis is conventionally divided into five phases:– Prophase, Prometaphase, Metaphase, Anaphase and Telophase

• Cytokinesis overlaps the latter stages of mitosis

–Interphase -cell growth and copying of chromosomes in preparation for cell division (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

Figure 12.6 The cell cycle.

BioFlix: Mitosis

G2 of Interphase Prophase Prometaphase

Centrosomes(with centriole pairs)

Chromatin(duplicated)

Nucleolus Nuclearenvelope

Plasmamembrane

Early mitoticspindle

AsterCentromere

Chromosome, consistingof two sister chromatids

Fragments of nuclearenvelope

Nonkinetochoremicrotubules

Kinetochore Kinetochoremicrotubule

Metaphase

Metaphase plate

Anaphase Telophase and Cytokinesis

Spindle Centrosome atone spindle pole

Daughterchromosomes

Cleavagefurrow

Nucleolusforming

Nuclearenvelopeforming

10

m

Figure 12.7 Exploring: Mitosis in an Animal Cell


Centrosomes(with centriole pairs)

Chromatin(duplicated)

NucleolusNuclearenvelope

Plasmamembrane

Early mitoticspindle

Aster

Centromere

Chromosome, consistingof two sister chromatids

Fragments of nuclearenvelope

Nonkinetochoremicrotubules

Kinetochore Kinetochoremicrotubule


• A nuclear envelope encloses the nucleus

• Nucleolus (nucleoli) are visible

• Centrosome (two centroles) duplicated, therefore two centrosomes

• Duplicated chromosomes have not yet condensed

• Chromatin is condensing into chromosomes

• Nucleolus (nucleoli) disappear• Duplicated chromosomes

appear as two identical sister chromatids

• Mitotic spindle begins to form, see asters

• Centrosome move away from each other

• Nuclear envelope fragments• Microtubules from centrosomes

invade nuclear area• Chromosomes more condensed,

have kinetochores• Microtubules attach to

kinetochores, become ‘kinetochores microtubules’

• Nonkinetochores microtubules interact with those of opposite pole of spindle

Metaphase

Metaphase plate

Anaphase Telophase and Cytokinesis

Spindle Centrosome atone spindle pole

Daughterchromosomes

Cleavagefurrow

Nucleolusforming

Nuclearenvelopeforming


• Centrosomes at opposite poles of the cells

• Chromosomes convened at metaphase plate, centromere lie at the metaphase plate

• For each chromosome, the kinetochores of the sister chromatids are attach to,kinetochores microtubules coming from opposite poles.

• Two daughter nuclei. Nuclear envelope arise.

• Nucleolus (nucleoli) reappear• Chromosomes are less

condensed • Remaining spindle microtubules

are depolymerized.• Mitosis, the nucleus division into

two identical nuclei is complete---------------------------------------------• Cytokinesis in animal cells is

sinchronized with telophase

• Shortest stage of mitosis• Sister chromatids of each pair

separate (each one now is a chromosome)

• Kinetochores microtubules shorten and chromosomes move toward opposite ends of the cell

• Nonkinetochores microtubules lengthen and the cell elongates

• End of anaphase, two complete equivalent collections of chromosomes


10

m


10

m

Metaphase Anaphase Telophase and Cytokinesis


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


• 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


Sisterchromatids

AsterCentrosome

Metaphaseplate(imaginary)

Kineto-chores

Overlappingnonkinetochoremicrotubules

Kinetochoremicrotubules

Microtubules

Chromosomes

Centrosome

0.5 m

1 m

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

Figure 12.8 The mitotic spindle at metaphase.

• 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


Figure 12.9 Inquiry: At which end do kinetochore microtubules shorten during anaphase?

Chromosomemovement

Microtubule

Motor protein

Chromosome

Kinetochore

Tubulinsubunits

Kinetochore

Mark

Spindlepole

EXPERIMENT

RESULTS

CONCLUSION

Chromosomemovement

Microtubule

Motor protein

Chromosome

Kinetochore

Tubulinsubunits

CONCLUSION

Figure 12.9 Inquiry: At which end do kinetochore microtubules shorten during anaphase?

• 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


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: Cytokinesis

Video: Sea Urchin (Time Lapse)

Video: Animal Mitosis

(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 m

1 m

Figure 12.10 Cytokinesis in animal and plant cells.

(a) Cleavage of an animal cell (SEM)

Cleavage furrow

Contractile ring ofmicrofilaments

Daughter cells

100 m


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

Vesiclesformingcell plate

Wall of parent cell

Cell plate New cell wall

Daughter cells

1 m


ChromatincondensingNucleus

Nucleolus Chromosomes Cell plate10 m

Prophase Prometaphase Metaphase Anaphase Telophase1 2 3 4 5

Figure 12.11 Mitosis in a plant cell.

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


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 Bacterial cell division by binary fission.

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


(a) Bacteria

(b) Dinoflagellates

(d) Most eukaryotes

Intact nuclearenvelope

Chromosomes

Microtubules

Intact nuclearenvelope

Kinetochoremicrotubule

Kinetochoremicrotubule

Fragments ofnuclear envelope

Bacterialchromosome

(c) Diatoms andsome yeasts

Figure 12.13 Mechanisms of cell division in several groups of organisms.

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 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


Experiment 1 Experiment 2

S

S S

G1 G1M

M M

EXPERIMENT

RESULTS

When a cell in the S phase was fused with a cell in G1,the G1 nucleus immediately Entered the S phase—DNAwas synthesized.

When a cell in the M phase was fused with a cell in G1, the G1nucleus immediatelybegan mitosis—a spindleformed and chromatincondensed, even thoughthe chromosome had notbeen duplicated.

Figure 12.14 Inquiry: Do molecular signals in the cytoplasm regulate the cell cycle?

Evidence for Cytoplasmic Signals

• 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


G1 checkpoint

G1

G2

G2 checkpointM checkpoint

M

SControlsystem

The Cell Cycle Control System

Figure 12.15 Mechanical analogy for the cell cycle control system.

G1 checkpoint

G1 G1

G0

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

• 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 12.16 The G1 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)

• 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


(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 SG1G2 G1

G2 G1

Cdk

Degradedcyclin

Cyclin isdegraded

MPF

G2checkpoint

Cdk

Cyclin

M

S

G1

G 2

Figure 12.17 Molecular control of the cell cycle at the G2 checkpoint.

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


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

3

4

Figure 12.18 The effect of platelet-derived growth factor (PDGF) on cell division.

Anchorage dependence

Density-dependent inhibition

Density-dependent inhibition

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

• 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


Figure 12.19 Density-dependent inhibition and anchorage dependence of cell division.

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 that are not eliminated by the immune system, 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 additional tumors


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

Figure 12.20 The growth and metastasis of a malignant breast tumor.


• Recent advances in understanding the cell cycle and cell cycle signaling have led to advances in cancer treatment– Intracellular receptors that can trigger cell division

• Herceptin (HER2)- cell-surface receptor tyrosine kinase hormone treatment• Estrogen Receptor (ER) treated with Tamoxifen

Figure 12.21 Impact: Advances in Treatment of Breast Cancer

Mitosis

Cytokinesis

MITOTIC (M) PHASE

G1

G2

S

Telophase andCytokinesis

AnaphaseMetaphase

Prometaphase

Prophase

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Figure 12.UN02

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Cap 12 - Ciclo Celular