Download Ap Chap 12 Cell Division

Chapter 12
The Cell Cycle
PowerPoint® Lecture Presentations for
Biology
Eighth Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-1
The Cell Cycle
Chapter 12 AP Bio
Overview: The Key Roles of Cell Division
• The ability of organisms to REPRODUCE
best distinguishes living things from
nonliving matter
• The continuity of life is based on the
reproduction of cells, or cell division
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Why do cells divide?
• 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
Fig. 12-2
100 µm
(a) Reproduction
20 µm
200 µm
(b) Growth and
development
(c) Tissue renewal
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-3
20 µm
• Every eukaryotic species has a
characteristic number of chromosomes in
each cell nucleus – not related to the
complexity of the organism
• Somatic cells (nonreproductive cells) have
two sets of chromosomes - diploid (2N). The
members of the pair are called homologous
chromosomes.
• Gametes (reproductive cells: sperm and
eggs) have half - haploid (1N) as many
chromosomes as somatic cells. They only
have one member of each pair.
23 pairs of homologous chromosomes in humans
in somatic cells
karyotype
What is a gamete?
Human gametes
have 23 chromosomes.
• Eukaryotic chromosomes consist of
chromatin, a complex of DNA and protein
that condenses during cell division
• In preparation for cell division, DNA is
replicated and the chromosomes condense
• Each duplicated chromosome has two
sister chromatids (identical DNA), which
separate during cell division
• The centromere is the narrow “waist” of the
duplicated chromosome, where the two
chromatids are most closely attached
Fig. 12-4
0.5 µm
Chromosomes
Chromosome arm
DNA molecules
Chromosome
duplication
(including DNA
synthesis)
Centromere
Sister
chromatids
Separation of
sister chromatids
Centromere
Sister chromatids
Fig. 12-UN3
Got this?
• Most cell division (mitosis) results in
daughter cells with identical genetic
information, DNA, and used for growth,
development, and repair
• A special type of division (meiosis)
produces nonidentical daughter cells
(gametes, or sperm and egg cells) with half
the number of chromosomes
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Eukaryotic cell division consists of:
– Mitosis, the division of the nucleus
– Cytokinesis, the division of the cytoplasm
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Phases of the Cell Cycle – period of growth and cell
division of the cell
• The cell cycle consists of
– Mitotic (M) phase (mitosis and cytokinesis)
– Interphase (cell growth and copying of
chromosomes in preparation for cell
division)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
• Interphase (about 90% of the cell cycle) can
be divided into subphases:
– G1 phase (“first gap”)
– S phase (“synthesis of DNA”)
– G2 phase (“second gap”)
• The cell grows during all three phases, but
chromosomes are duplicated only during
the S phase.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-5
G1
S
(DNA synthesis)
G2
Fig. 12-UN1
G1
S
Cytokinesis
Mitosis
G2
MITOTIC (M) PHASE
Prophase
Telophase and
Cytokinesis
Prometaphase
Anaphase
Metaphase
What happens in each phase:
What is the Go stage?
• Cells that do not normally divide or for various
reasons, are not preparing to divide, enter a
state of arrest.
Ex: - nerve cells, muscle cells, rbc’s
- cells that are starved of nutrients, densityinhibited, or treated with growth inhibitors
The Stages of Mitosis
• Mitosis is conventionally divided into five
phases:
– Prophase
– Prometaphase
– Metaphase
– Anaphase
– Telophase
• Cytokinesis (division of the cytoplasm) is
well underway by late telophase.
•Watch bioflix
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
What is the purpose of mitosis?
• To produce two genetically identical cells –
ie, have the same number of chromosomes
as the original cell.
• Occurs in eukaryotic multicellular somatic
cells for growth, development, and repair.
• In unicellular organisms, it is a method of
asexual reproduction.
Fig. 12-UN6
One
chromosome
Fig. 12-6
G2 of Interphase
Centrosomes
Chromatin
(with centriole (duplicated)
pairs)
Prophase
Early mitotic Aster Centromere
spindle
Nucleolus Nuclear Plasma
envelope membrane
Chromosome, consisting
of two sister chromatids
Metaphase
Prometaphase
Fragments Nonkinetochore
of nuclear
microtubules
envelope
Kinetochore
Kinetochore
microtubule
Anaphase
Cleavage
furrow
Metaphase
plate
Spindle
Centrosome at
one spindle pole
Telophase and Cytokinesis
Daughter
chromosomes
Nuclear
envelope
forming
Nucleolus
forming
Fig. 12-6a
G2 of Interphase
Prophase
Prometaphase
Fig. 12-6b
G2 of Interphase
Chromatin
Centrosomes
(with centriole (duplicated)
pairs)
Prophase
Early mitotic Aster
spindle
Nucleolus Nuclear Plasma
envelope membrane
Prometaphase
Centromere
Chromosome, consisting
of two sister chromatids
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
Fig. 12-6c
Metaphase
Anaphase
Telophase and Cytokinesis
Fig. 12-6d
Metaphase
Anaphase
Metaphase
plate
Spindle
Centrosome at
one spindle pole
Telophase and Cytokinesis
Cleavage
furrow
Daughter
chromosomes
Nuclear
envelope
forming
Nucleolus
forming
PROPHASE
• Chromosomes condense, nuclear membrane
and nucleoli disappear, spindle fibers (made
of microtubules) form.
Fig. 12-6b
G2 of Interphase
Chromatin
Centrosomes
(with centriole (duplicated)
pairs)
Prophase
Early mitotic Aster
spindle
Nucleolus Nuclear Plasma
envelope membrane
Prometaphase
Centromere
Chromosome, consisting
of two sister chromatids
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
In animal cells:
• Spindle fibers form in the centrosome (the
microtubule organizing center), also contains
the centrioles.
•The centrosome replicates and migrate to
opposite ends of the cell, as spindle
microtubules grow out from them
•An aster (a radial array of short microtubules
in animal cells) extends from each centrosome
– used for stability.
In animal cells:
PROMETAPHASE AND METAPHASE
• During prometaphase, some spindle
microtubules attach to the kinetochores of
chromosomes and begin to move the
chromosomes
• At metaphase, the chromosomes are all
lined up at the metaphase plate, the midway
point between the spindle’s two poles
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-7
Aster
Centrosome
Sister
chromatids
Microtubules
Chromosomes
Metaphase
plate
Kinetochores
Centrosome
1 µm
Overlapping
nonkinetochore
microtubules
Kinetochore
microtubules
0.5 µm
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-8a
EXPERIMENT
Kinetochore
Spindle
pole
Mark
RESULTS
Notice
the shortening of
the spindle fibers
Fig. 12-8b
CONCLUSION
Chromosome
movement
Kinetochore
Microtubule
Motor
protein
Chromosome
Tubulin
Subunits
TELOPHASE
• In telophase, genetically identical daughter
nuclei form at opposite ends of the cell
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-9a
100 µm
Cleavage furrow
Contractile ring of
microfilaments
Daughter cells
(a) Cleavage of an animal cell (SEM)
Fig. 12-9b
Vesicles
forming
cell plate
Wall of
parent cell
Cell plate
1 µm
New cell wall
Daughter cells
(b) Cell plate formation in a plant cell (TEM)
Fig. 12-10
Plant Cell Mitosis
Nucleus
Nucleolus
1 Prophase
Chromatin
condensing
Chromosomes
2 Prometaphase
•http://www.foothilltech.org/rduston/uploadth
eseworksheets/biology/Mitosis%20and%20Me
iosis/Mitosis_Cell%20Cycle/12-05AnimalMitosisVideo-S.mov
3 Metaphase
Cell plate
4 Anaphase
5 Telophase
10 µm
Fig. 12-10a
Nucleus
Nucleolus
1 Prophase
Chromatin
condensing
Fig. 12-10b
Chromosomes
2 Prometaphase
Fig. 12-10c
3 Metaphase
Fig. 12-10d
4 Anaphase
Fig. 12-10e
Cell plate
5 Telophase
10 µm
Fig. 12-UN2
•1
2
3
4
5
6
7
8
9
16
15
10
14
13
11
12
Fig. 12-UN5
Interphase
Mitosis in a living cell
•LabBench
Binary Fission
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-11-1
Cell wall
Origin of
replication
E. coli cell
Two copies
of origin
Plasma
membrane
Bacterial
chromosome
Fig. 12-11-2
Cell wall
Origin of
replication
E. coli cell
Two copies
of origin
Origin
Plasma
membrane
Bacterial
chromosome
Origin
Fig. 12-11-3
Cell wall
Origin of
replication
E. coli cell
Two copies
of origin
Origin
Plasma
membrane
Bacterial
chromosome
Origin
Fig. 12-11-4
Cell wall
Origin of
replication
E. coli cell
Two copies
of origin
Origin
Plasma
membrane
Bacterial
chromosome
Origin
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
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Fig. 12-12
Bacterial
chromosome
(a) Bacteria
Chromosomes
Microtubules
Intact nuclear
envelope
(b) Dinoflagellates
Nuclear envelope
stays intact.
Kinetochore
microtubule
Intact nuclear
envelope
(c) Diatoms and yeasts
Kinetochore
microtubule
Fragments of
nuclear envelope
(d) Most eukaryotes
No nuclear envelope
Mitosis Graph
Number of
chromatids/
chromosomes
G1
S
G2
Prophase
Metaphase
Anaphase
Telophase
1c
Relative number Relative amount
of
of DNA/cell
chromsomes/cell
2N
2X
4n
Relative
Amt of
3n
DNA/cell
2n
1n
Time in hours
meristematic area
Ascaris Eggs Mitosis
What stages?
Equatorial plate view
The eukaryotic cell cycle is regulated by a
molecular control system
• The frequency of cell division varies with
the type of cell
• These cell cycle differences result from
regulation at the molecular level
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Evidence for Cytoplasmic Signals
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-13
EXPERIMENT
Experiment 1
S
G1
Experiment 2
M
G1
RESULTS
S
S
When a cell in the
S phase was fused
with a cell in G1, the G1
nucleus immediately
entered the S
phase—DNA was
synthesized.
M
M
When a cell in the
M phase was fused with
a cell in G1, the G1
nucleus immediately
began mitosis—a
spindle formed and
chromatin condensed,
even though the
chromosome had not
been duplicated.
The Cell Cycle Control System is like a clock
• The cell cycle “clock” has specific
checkpoints where the cell cycle stops until
a go-ahead signal is received
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-14
G1 checkpoint
Control
system
G1
M
G2
M checkpoint
G2 checkpoint
S
• 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
G0
G1 checkpoint
G1
(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)
• Cyclin + Cdk = MPF
• The activity of cyclins and Cdks fluctuates
during the cell cycle
• MPF (maturation-promoting factor) pushes
the cell past the G2 checkpoint into the M
phase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-16
RESULTS
5
30
4
20
3
2
10
1
0
100
0
500
400
300
Time (min)
Notice that as kinase increases, so does cell division.
200
Fig. 12-17a
M
G1
S
G2
M
G1
S
G2
M
G1
MPF activity
Cyclin
concentration
Time
(a) Fluctuation of MPF activity and cyclin concentration during
the cell cycle
MPF (maturation-promoting factor) pushes the
cell past the G2 checkpoint into the M phase
Fig. 12-17b
Degraded
cyclin
G2
Cdk
checkpoint
Cyclin is
degraded
MPF
Cyclin
(b) Molecular mechanisms that help regulate the cell cycle
Cyclin accumulation
Cdk
External Signals:
•
Growth Factors – example platelet derived
growth factor PDGF
•
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 12-18
Experiment with Growth Factors
Scalpels
Petri
plate
Without PDGF
cells fail to divide
With PDGF
cells proliferate
Cultured fibroblasts
10 µm
Fig. 12-19
Anchorage dependence
Density-dependent inhibition
Density-dependent inhibition
25 µm
25 µm
(a) Normal mammalian cells
(b) Cancer cells
• Cancer cells exhibit neither densitydependent inhibition nor anchorage
dependence
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
p53 genes and p27 genes in cancer
• p53 is a protein that functions to block the cell cycle
if the DNA is damaged. If the damage is severe this
protein can cause apoptosis (cell death).
• p53 levels are increased in damaged cells. This allows
time to repair DNA by blocking the cell cycle.
• A p53 mutation is the most frequent mutation leading
to cancer.
• p27 is a protein that binds to cyclin and cdk blocking
entry into S phase. Recent research suggests that
breast cancer prognosis is determined by p27 levels.
Reduced levels of p27 predict a poor outcome for
breast cancer patients.
Internal Signals
• An example of an internal signal is that
kinetochores not attached to spindle
microtubules send a molecular signal that
delays anaphase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
What about telomeres?
• The number of times a cell divides is
determined by special segments of DNA
called telomeres, which are located at the
ends of each chromosome. Every time a cell
divides, the telomeres get shorter. When
they are reduced to a certain length, the cell
stops dividing.
The Hayflick Limit
• The Hayflick limit (or Hayflick Phenomena)
is the number of times a normal cell
population will divide before it stops,
presumably because the telomeres reach a
critical length.
• Hayflick demonstrated that a population of
normal human fetal cells in a cell culture
divide between 40 and 60 times. It then
enters a senescence phase.
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
•HHMI's BioInteractive - Angiogenesis
• 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
Fig. 12-20
Lymph
vessel
Tumor
Blood
vessel
Cancer
cell
Metastatic
tumor
Glandular
tissue
1 A tumor grows
from a single
cancer cell.
2 Cancer cells
invade neighboring tissue.
3 Cancer cells spread
to other parts of
the body.
4 Cancer cells may
survive and
establish a new
tumor in another
part of the body.
So, how do cancer drugs work?
Categories of Chemotherapy Drugs:
1) Stop the synthesis of pre DNA molecule
building blocks – this includes folic acid
and nucleotides
• Examples of drugs in this class include
methotrexate (Abitrexate®), fluorouracil
(Adrucil®), hydroxyurea (Hydrea®), and
mercaptopurine (Purinethol®).
2) Directly damage the DNA in the nucleus
of the cell:
They disrupt replication of the DNA and
either totally halt replication or cause the
manufacture of nonsense DNA or RNA (i.e.
the new DNA or RNA does not code for
anything useful).
Examples of drugs in this class include
cisplatin (Platinol®) and antibiotics daunorubicin (Cerubidine®), doxorubicin
(Adriamycin®), and etoposide (VePesid®).
3) Affect the synthesis or breakdown of the
mitotic spindles.
Examples of drugs in this class of mitotic
disrupters include: Vinblastine (Velban®),
Vincristine (Oncovin®) and Pacitaxel
(Taxol®).
Other targets would be
4) Disrupt hormones that turn on cell division
5) Boost the immune system
6) Interfere with telomeres (cancer cells have
telomerase, an enzyme which can add
length to their telomeres so they can divide
longer)
7) Block binding sites for proteins (enzymes)
• The drug Gleevec has been designed to
disrupt the growth of leukemia cells by
blocking a binding site of a key protein
found only in tumor cells and not in normal
cells.
• The growth of leukemia cells is stimulated
when the mutant cancer enzyme BCR-ABL
phosphorylates (from ATP) a substrate
protein. This causes the substrate to
change shape. It can then go on to stimulate
leukemia cell growth.
• Gleevec's shape mimics ATP, and binds to
the same site on BCR-ABL that ATP
normally occupies. Gleevec thus prevents
phosphorylation of the substrate protein,
and inhibits leukemia cell growth.
•HHMI's BioInteractive - Gleevec
Unfortunately, the majority of drugs currently
on the market are not specific, which leads to
the many common side effects associated with
cancer chemotherapy.
Since the drugs are not specific to recognize
normal cells from cancerous cells, the side
effects are seen in bodily systems that
naturally have a rapid turnover of cells
including skin, hair, gastrointestinal, and bone
marrow. These healthy, normal cells, also end
up damaged by the chemotherapy program.
Using modified viruses to kill cancer cells
• Using the p53 gene to fight cancer
•HHMI's BioInteractive - p53
•HHMI's BioInteractive - Using p53 to Fight Cancer
Case Study: The Immortal Cells of Henrietta Lacks
•http://www.cbsnews.com/83013445_162-6300824/the-immortalhenrietta-lacks/
• Part I: The HeLa Cells
• Part II: The Family
• Part III: Henrietta’s Cancer Cells
• Part IV: The Continuing Story:
Henrietta’s Genome
•http://www.cbsnews.com/8301-3445_1626300824/the-immortal-henrietta-lacks/
•http://www.foxnews.com/opinion/2013/08/26/scientificbreakthroughs-vs-your-privacy-lessons-from-henriettalacks-saga/
Should Henrietta’s genome be private?
•http://www.foxnews.com/opinion/2013/08/2
6/scientific-breakthroughs-vs-your-privacylessons-from-henrietta-lacks-saga/