Biology Sylvia S. Mader Michael Windelspecht Chapter 9 The Cell Cycle and Cellular Reproduction...

BiologySylvia S. Mader

Michael Windelspecht

Chapter 9The Cell Cycle and

Cellular Reproduction

Lecture Outline

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

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Outline

• 9.1 The Cell Cycle

• 9.2 Mitosis and Cytokinesis

• 9.3 The Cell Cycle and Cancer

• 9.4 Prokaryotic Cell Division

2

9.1 The Cell Cycle

• The cell cycle is an orderly set of stages from the first division to the time the resulting daughter cells divide

• Just prior to the next division: The cell grows larger The number of organelles doubles The DNA is replicated

• The two major stages of the cell cycle: Interphase (includes several stages) Mitotic Stage (includes mitosis and cytokinesis)

3

The Cell Cycle

4


G1

(growth)G0

G2 checkpointMitosis checkpoint.Mitosis will occurif DNA hasreplicated properly.Apoptosis willoccur if the DNA isdamaged andcannot be repaired.

S(growth and DNA

replication)

M

Cytokinesis

Telo

phas

eA

nap

has

e

Met

aph

ase

Late

pro

phas

e

Prophase

Interphase

G1 checkpointCell cycle main checkpoint.If DNA is damaged, apoptosiswill occur. Otherwise, the cellis committed to divide whengrowth signals are presentand nutrients are available.

M checkpointSpindle assemblycheckpoint. Mitosiswill not continue ifchromosomes arenot properly aligned.

M

G2

G1

G2

(growth and finalpreparations for

division)

The Cell Cycle

• Interphase Most of the cell cycle is spent in

interphase Cell performs its usual functions Time spent in interphase varies by cell

type Nerve and muscle cells do not complete

the cell cycle (remain in the G0 stage)

5

The Cell Cycle

• Interphase consists of: G1, S, and G2 phases G1 Phase:

• Recovery from previous division• Cell doubles its organelles• Cell grows in size• Cell accumulates raw materials for DNA synthesis

S Phase:• DNA replication • Proteins associated with DNA are synthesized • Chromosomes enter with 1 chromatid each• Chromosomes leave with 2 identical chromatids (sister

chromatids) each G2 Phase:

• Between DNA replication and onset of mitosis• Cell synthesizes proteins necessary for division

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The Cell Cycle

• M (Mitotic) Stage Includes:

• Mitosis – Nuclear division

– Daughter chromosomes are distributed by the mitotic spindle to two daughter nuclei

• Cytokinesis– Division of the cytoplasm

Results in two genetically identical daughter cells

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The Cell Cycle

• The cell cycle is controlled by internal and external signals

• A signal is a molecule that either stimulates or inhibits a metabolic event. Internal signals

• Family of proteins called cyclins that increase and decrease as the cell cycle continues

• Without cyclins, the cell cycle stops at G1, M or G2 (checkpoints)

• Allows time for any damage to be repaired

8

The Cell Cycle

• Apoptosis is programmed cell death• It involves a sequence of cellular events:

fragmenting of the nucleus, blistering of the plasma membrane engulfing of cell fragments.

• Apoptosis is caused by enzymes called caspases.

• Mitosis and apoptosis are opposing forces Mitosis increases cell number Apoptosis decreases cell number

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Apoptosis

10


apoptotic cell

cellfragment

DNAfragment

Cell roundsup, and nucleuscollapses.

Chromatincondenses, andnucleus fragments.

Plasma membraneblisters, and blebsform.

Cell fragmentscontain DNAfragments.

blebs

Courtesy Douglas R. Green/LaJolla Institute for Allergy and Immunology

The Cell Cycle

• Apoptosis Cells harbor caspases that are kept in

check by inhibitors• Can be unleashed by internal or external

signals Signal protein p53

• Stops the cell cycle at G1 when DNA is damaged

• Initiates an attempt at DNA repair–If successful, the cycle continues to

mitosis–If not, apoptosis is initiated

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Regulation at the G1 Checkpoint

12


a.

PP

RBprotein

RBprotein

E2FE2F E2F

CDKnot present

E2F not releasedreleased

E2F

E2F binds to DNA.

DNA

cell cycleproteins

phosphorylated RB

CDK present

b.

P

P

P P

breakdownof p53

no DNAdamage

DNAdamage

phosphorylated p53DNA repairproteins

apoptosis

p53 binds to DNA.

DNA DNA

p53

9.2 Mitosis and Cytokinesis

• DNA is in very long threads Chromosomes Stretched out and intertwined between divisions DNA is associated with histones (proteins) DNA and histone proteins are collectively called

chromatin

• Before mitosis begins: Chromatin condenses (coils) into distinctly

visible chromosomes Each species has a characteristic

chromosome number

13

14

Diploid Chromosome Numbers of Some Eukaryotes

Mitosis and Cytokinesis

• The diploid (2n) number includes two sets of chromosomes of each type Humans have 23 different types of

chromosomes• Each type is represented twice in each body cell

(diploid)• Only sperm and eggs have one of each type

·termed haploid (n) The haploid (n) number for humans is 23

• Two representatives of each chromosome type• Makes a total of 2n = 46 in each nucleus

– One set of 23 from individual’s father (paternal)– Other set of 23 from individual’s mother (maternal)

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• At the end of S phase: Each chromosome internally duplicated Consists of two identical DNA chains

• Sister chromatids (two strands of genetically identical chromosomes)

• Attached together at a single point (called centromere)

• During mitosis: Centromeres holding sister chromatids together

separate Sister chromatids separate Each becomes a daughter chromosome Sisters of each type are distributed to opposite

daughter nuclei

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Duplicated Chromosomes

17


centromere

sister chromatids

one chromatida. b.

kinetochore

9,850© Andrew Syred/Photo Researchers, Inc.


• Just outside the nucleus is the centrosome This is the microtubule organizing center in animal

cells Organizes the mitotic spindle

• Contains many fibers• Each fiber is composed of a bundle of microtubules

In animals, the centrosome contains two barrel-shaped centrioles

• Oriented at right angles to each other within the centrosome• Each has 9 triplets of microtubules arranged in a cylinder

• Centrosome was also replicated in S-phase, so there are two centrosomes before mitosis begins

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• Phases of Mitosis: Prophase

• Chromatin has condensed– Chromosomes are distinguishable with microscope

– Each chromosome has two sister chromatids attached at the centromere

• Nucleolus disappears

• Nuclear envelope disintegrates

• Spindle begins to assemble

• The two centrosomes move away from each other

• Microtubules form star-like arrays termed asters

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• Phases of Mitosis

Prometaphase

• The centromere of each chromosome develops two kinetochores

– Specialized protein complex

– One attached to each sister chromatid

» Physically connect sister chromatids with specialized microtubules (kinetochores)

» These connect sister chromatids to opposite poles of the mother cell

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• Stages of Mitosis Metaphase

• Chromosomes are pulled around by kinetochore fibers

• Forced to align across the equatorial plane of the cell

– Metaphase plate - Represents plane through which mother cell will be divided

Anaphase• Centromere dissolves, releasing sister chromatids

• Sister chromatids separate

– Now called daughter chromosomes

– Pulled to opposite poles along kinetochore fibers

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• Stages of Mitosis Telophase

• Spindle disappears

• Now two clusters of daughter chromosomes

– Still two of each type with all types represented

– Clusters are incipient daughter nuclei

• Nuclear envelopes form around the two incipient daughter nuclei

– Each daughter nucleus receives one chromosome of each type

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• Cytokinesis = division of cytoplasm• Allocates the mother cell’s cytoplasm equally to

daughter nucleus• Encloses each daughter cell in its own plasma

membrane• Often begins in anaphase• Animal cytokinesis:

A cleavage furrow appears between daughter nuclei Formed by a contractile ring of actin filaments Like pulling on a drawstring Eventually pinches the mother cell in two

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• Cytokinesis in plant cells begins with the formation of a cell plate Rigid cell walls outside plasma membrane do not

permit furrowing Many small membrane-bounded vesicles Eventually fuse into one thin vesicle extending across

the mother cell The membranes of the cell plate become the plasma

membrane between the daughter cells The space between the daughter cells becomes filled

with the middle lamella Daughter cells later secrete primary cell walls on

opposite sides of the middle lamella

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Cytokinesis in Animal Cells

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Cleavage furrow

Contractile ring

X 4,000

X 4,000

(top): © Thomas Deerinck/Visuals Unlimited; (bottom): © SPL/Getty RF

Cytokinesis in Plant Cells

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daughter cells

nucleoli

daughternucleus

cell plate formation

daughter nucleus

vesicles containingmembrane componentsfusing to form cell plate

(left): © B.A. Palevitz and E.H. Newcomb/BPS/Tom Stack & Associates

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Phases of Mitosis in Animal and Plant Cells


Animal cell(Early prophase, Prophase, Metaphase, Anaphase, Telophase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.;Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unlimited; Plant cell(Telophase): © Jack M.

Bostrack/Visuals Unlimited;

Plant Cellat Interphase

centromere

aster

kinetochore

polar spindle fiber

chromosomescell wall25µm

centrosome

lacks centrioles

MIT

OS

IS

centrosomehas centrioles

Animal Cellat Interphase

nuclearenvelopefragments

chromatincondenses

nucleolusdisappears

Early ProphaseCentrosomes have duplicated.Chromatin is condensing into

chromosomes, and the nuclearenvelope is fragmenting.

ProphaseNucleolus has disappeared, and

duplicated chromosomes are visible.Centrosomes begin moving apart,

and spindle is in process of forming.




20 µm duplicatedchromosome

20 µm

spindlefibers forming

spindlepole

9 µm

kinetochorespindle fiber

cleavage furrow

spindle fibers

20µm 16µm


AnaphaseSister chromatids part and become daughterchromosomes that move toward the spindle

poles. In this way, each pole receives the samenumber and kinds of chromosomes as the parent cell.

MetaphaseCentromeres of duplicated chromosomesare aligned at the metaphase plate (center

of fully formed spindle). Kinetochore spindlefibers attached to the sister chromatids

come from opposite spindle poles.

chromosomes atmetaphase plate

6.2µm6.2µm20µm6.2µmspindle pole lackscentrioles and aster

TelophaseDaughter cells are formingas nuclear envelopes and

nucleoli reappear. Chromosomes willbecome indistinct chromatin.

daughter chromosome 20µm

nucleolus

cell plate 6.6µm


Animal cell(Early prophase): © Ed Reschke; Plant cell(Early prophase): © Ed Reschke


Early Prophase

aster20 µm

25 µm

MIT

OS

IS

Early Prophase

Centrosomes have duplicated.

Chromatin is condensing into

chromosomes, and the nuclear

envelope is fragmenting.

chromatincondenses

nucleolusdisappears




centrosomelacks centrioles


Phases of Mitosis in Animal and Plant Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Animal cell(Early prophase, Prophase): © Ed Reschke; Plant cell(Early prophase): © Ed Reschke; Plant cell(Prophase): © R. Calentine/Visuals Unlimited

Prophase


centromere

aster

chromosomescell wall

20 µm 20 µm

6.2 µm25 µm

Prophase

Nucleolus has disappeared, and

duplicated chromosomes are

visible. Centrosomes begin moving

apart, and spindle is in process

of forming.MIT

OS

IS





chromatincondenses

nucleolusdisappears



duplicatedchromosome




Animal cell(Early prophase, Prophase, Metaphase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.;Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase): © R. Calentine/Visuals Unlimited

Prometaphase

centromere

spindlepole

aster

kinetochore

polar spindle fiber


20 µm 20 µm

6.2 µm25 µm 20 µm

9 µm

Prometaphase

The kinetochore of each

chromatid is attached to a

kinetochore spindle fiber. Polar

spindle fibers stretch from each

spindle pole and overlap.




chromatincondenses

nucleolusdisappears









spindle pole lackscentrioles and aster



MIT

OS

IS



Animal cell(Early prophase, Prophase, Metaphase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.;Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase): © R. Calentine/Visuals Unlimited


centromere

aster

kinetochore

polar spindle fiber


20 µm

6.2 µm25 µm 20 µm

9 µm

spindle fibers

20 µm

6.2 µm

Metaphase

Centromeres of duplicated

chromosomes are aligned at the

metaphase plate (center of fully

formed spindle). Kinetochore

spindle fibers attached to the

sister chromatids come from

opposite spindle poles.




nucleolusdisappears

chromatincondenses







PrometaphaseThe kinetochore of each chromatid is

attached to a kinetochore spindle fiber.Polar spindle fibers stretch from each


Metaphase



spindlepole

kinetochorespindle fiberspindle

fibers forming



MIT

OS

IS

20 µm



Animal cell(Early prophase, Prophase, Metaphase, Anaphase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.;Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unlimited

centromere

spindlepole

aster

kinetochore


polar spindle fiber


20 µm 20 µm

6.2 µm25 µm 20 µm

9 µmdaughter chromosome

spindle fibers

20 µm 20 µm

6.2 µm6.2 µm




nucleolusdisappears

chromatincondenses














Anaphase






MIT

OS

IS

Anaphase

Sister chromatids part and become

daughter chromosomes that move

toward the spindle poles. In this

way, each pole receives the same

number and kinds of chromosomes

as the parent cell.



centromere

aster

kinetochore

polar spindle fiber


20 µm 20 µm

6.2 µm25 µm 20 µm

9 µm daughter chromosome

spindle fibers cell plate

20 µm 20 µm 16 µm

6.2 µm 6.6 µm6.2 µm

nucleolus

cleavage furrow

Telophase

Daughter cells are forming

as nuclear envelopes and

nucleoli reappear.

Chromosomes will

become indistinct chromatin.




chromatincondensesnucleolusdisappears

















AnaphaseSister chromatids part and become daughterchromosomes that move toward the spindle

poles. In this way, each pole receives the samenumber and kinds of chromosomes as the parent cell.

Telophase


spindlepole



Animal cell(Early prophase, Prophase, Metaphase, Anaphase, Telophase): © Ed Reschke; Animal cell(Prometaphase): © Michael Abbey/Photo Researchers, Inc.; Plant cell(Early prophase, Prometaphse): © Ed Reschke; Plant cell(Prophase, Metaphase, Anaphase): © R. Calentine/Visuals Unlimited; Plant cell(Telophase): © Jack M. Bostrack/Visuals Unlimited;

MIT

OS

IS


• Functions of mitosis: Permits growth and repair. In flowering plants, meristematic tissue

retains the ability to divide throughout the life of the plant

In mammals, mitosis is necessary when:• A fertilized egg becomes an embryo • An embryo becomes a fetus• A cut heals or a broken bone mends

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• Stem Cells Many mammalian organs contain stem cells

• Retain the ability to divide • Red bone marrow stem cells divide to produce various

types of blood cells

Therapeutic cloning to produce human tissues can begin with either adult stem cells or embryonic stem cells

Embryonic stem cells can be used for reproductive cloning, the production of a new individual

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Reproductive and Therapeutic Cloning

36


remove anddiscard eggnucleusegg

removeGo nucleus

Go cells fromanimal to becloned

egg

fuse eggwith Go

nucleus

Implantembryo

intosurrogate

mother

Clone is born

culture

embryonicstem cells

nervous

blood

muscleembryonicstem cells

culture

fuse eggwith Go

nucleus

remove anddiscard eggnucleus

Go somatic cells

removeGo nucleus

b. Therapeutic cloning

a. Reproductive cloning

9.3 The Cell Cycle and Cancer

• Abnormal growth of cells is called a tumor Benign tumors are not cancerous

• Encapsulated• Do not invade neighboring tissue or spread

Malignant tumors are cancerous• Not encapsulated• Readily invade neighboring tissues• May also detach and lodge in distant places (metastasis)• Results from mutation of genes regulating the cell cycle

• Development of cancer Tends to be gradual May take years before a cell is obviously cancerous

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The Cell Cycle and Cancer

• Characteristics of Cancer Cells Lack differentiation

• Are non-specialized• Are immortal (can enter cell cycle repeatedly)

Have abnormal nuclei• May be enlarged• May have abnormal number of chromosomes• Often have extra copies of genes

Do not undergo apoptosis• Normally, cells with damaged DNA undergo apoptosis• The immune system can also recognize abnormal cells and

trigger apoptosis• Cancer cells are abnormal but fail to undergo apoptosis

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• Characteristics of Cancer Cells Form tumors

• Mitosis is normally controlled by contact with neighboring cells – contact inhibition

• Cancer cells have lost contact inhibition Undergo metastasis

• Original tumor easily fragments• New tumors appear in other organs

Undergo angiogenesis• Formation of new blood vessels

– Brings nutrients and oxygen to the tumor

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Progression of Cancer

40


primary tumor

New mutations arise, and one cell (brown) has the ability to start a tumor.

Cancer in situ. The tumor is at its place of origin. One cell (purple)mutates further.

Cancer cells now have the ability to invade lymphatic and blood vesselsand travel throughout the body.

New metastatic tumors are found some distance from the primary tumor.

lymphaticvessel

bloodvessel

lymphaticvessel

bloodvessel

Cancer Cells vs. Normal Cells

41


• Origin of Cancer Oncogenes

• Proto-oncogenes promote the cell cycle in various ways

• If a proto-oncogene is mutated, it may become an oncogene

Tumor suppressor genes inhibit the cell cycle in various ways

• If a tumor suppressor gene becomes inactive, it may promote cancer development

Both proto-oncogenes and tumor suppressor genes are normally regulated in coordination with organism’s growth plan

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• Origin of Cancer Chromosomes normally have special material

at each end called telomeres These get shorter each cell division When they get very short, the cell will no

longer divide Telomerase is an enzyme that maintains the

length of telomeres Mutations in telomerase gene:

• Cause telomeres to continue to lengthen, which• Allows cancer cells to continually divide

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Causes of Cancer

44


d: © Biophoto Associates/Photo Researchers, Inc.

activatedsignalingprotein

growthfactor

receptorprotein

signalingprotein

phosphate

b. Effect of growth factor

P

P

P

proto-oncogeneCodes for a growth factor,a receptor protein, or asignaling protein in astimulatory pathway.If a proto-oncogenebecomes an oncogene,the end result can beactive cell division.

tumor suppressor geneCodes for a signalingprotein in an inhibitorypathway. If a tumorsuppressor gene mutates,the end result can beactive cell division.

c. Stimulatory pathway andinhibitory pathway

1,100Xd. Cancerous skin cell

gene productpromotescell cycle

Stimulatorypathway

Inhibitorypathway

gene productinhibitscell cycle

growth factorActivates signalingproteins in a stimulatorypathway that extendsto the nucleus.

a. Influences that cause mutated proto-oncogenes(called oncogenes) and mutated tumorsuppressor genes

Heredity Radiationsources

Pesticides and

herbicides

Viruses

oncogene

9.4 Prokaryotic Cell Division

• The prokaryotic chromosome is a ring of DNA Folded up in an area called the nucleoid 1,000 X the length of cell Replicated into two rings prior to cell division Replicated rings attach to the plasma membrane

• Binary fission Splitting in two Two replicate chromosomes are distributed to two

daughter cells Produces two daughter cells identical to original cell –

asexual reproduction

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Binary Fission

46


chromosome

cell wall

plasmamembrane

cytoplasm

SEM 2,345X

1. Attachment of chromosome toa special plasma membranesite indicates that thisbacterium is about to divide.

© Dennis Kunkel Microscopy, Inc./Visuals Unlimited

Binary Fission

47


chromosome

cell wall

plasmamembrane

cytoplasm

SEM 2,345X


2. The cell is preparing for binaryfission by enlarging its cell wall,plasma membrane, and overallvolume.


Binary Fission

48


chromosome

cell wall

plasmamembrane

cytoplasm

SEM 2,345X



3. DNA replication has producedtwo identical chromosomes.Cell wall and plasma membrane begin to grow inward.


Binary Fission

49


chromosome

cell wall

plasmamembrane

cytoplasm

SEM 2,345X© Dennis Kunkel Microscopy, Inc./Visuals Unlimited




4. As the cell elongates, thechromosomes are pulled apart.Cytoplasm is being distributedevenly.

Binary Fission

50





4. As the cell elongates, thechromosomes are pulled apart.Cytoplasm is being distributedevenly.

5. New cell wall and plasmamembrane has divided thedaughter cells.

chromosome

cell wall

plasmamembrane

cytoplasm

SEM 2,345X© Dennis Kunkel Microscopy, Inc./Visuals Unlimited

Functions of Cell Division

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Biology Sylvia S. Mader Michael Windelspecht Chapter 9 The Cell Cycle and Cellular Reproduction...

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