Download Cell Cycle

The Cell Cycle and How Cells Divide
1
Phases of the Cell Cycle
•
The cell cycle consists of
– Interphase – normal cell activity
– The mitotic phase – cell divsion
INTERPHASE
Growth
G1
(DNA synthesis)
Growth
G2
2
Functions of Cell Division
100 µm
(a) Reproduction. An amoeba,
a single-celled eukaryote, is
dividing into two cells. Each
new cell will be an individual
organism (LM).
200 µm
20 µm
(b) Growth and development.
(c) Tissue renewal. These dividing
This micrograph shows a
bone marrow cells (arrow) will
sand dollar embryo shortly after
give rise to new blood cells (LM).
the fertilized egg divided, forming
two cells (LM).
3
Cell Division
•
•
•
An integral part of the cell cycle
Results in genetically identical daughter cells
Cells duplicate their genetic material
– Before they divide, ensuring that each daughter
cell receives an exact copy of the genetic
material, DNA
4
DNA
•
•
Genetic information - genome
Packaged into chromosomes
Figure 12.3
50 µm
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DNA And Chromosomes
•
•
An average eukaryotic cell has about 1,000
times more DNA then an average
prokaryotic cell.
The DNA in a eukaryotic cell is organized
into several linear chromosomes, whose
organization is much more complex than the
single, circular DNA molecule in a
prokaryotic cell
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DNA And Chromosomes
Prokaryotes
Structure Single, naked, circular
DNA molecule; attached
to 1 point on the inner
surface of plasma
membrane
Location
In an area of the
cytoplasm called the
nucleoid
Eukaryotes
Many linear
chromosomes, each
made of 1 DNA
molecule joined with
protein
Inside a membranebound nucleus
7
Chromosomes
•
All eukaryotic cells store genetic information
in chromosomes.
– Most eukaryotes have between 10 and 50
chromosomes in their body cells.
– Human cells have 46 chromosomes.
– 23 nearly-identical pairs
8
Structure of Chromosomes
•
•
•
Chromosomes are composed of a
complex of DNA and protein called
chromatin that condenses during cell
division
DNA exists as a single, long, doublestranded fiber extending chromosome’s
entire length.
Each unduplicated chromosome contains
one DNA molecule, which may be
several inches long
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Structure of Chromosomes
 Every 200 nucleotide pairs, the DNA wraps twice around a
group of 8 histone proteins to form a nucleosome.
 Higher order coiling and supercoiling also help condense
and package the chromatin inside the nucleus:
10
Structure of Chromosomes
The degree of coiling can vary in different
regions of the chromatin:
Heterochromatin refers to highly coiled
regions where genes aren’t expressed.
Euchromatin refers to loosely coiled regions
where genes can be expressed.
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Structure of Chromosomes
•
•
•
Prior to cell division each
chromosome duplicates
itself.
During this time, only the
heterochromatin is visible, as
dense granules inside the
nucleus.
There is also a dense area of
RNA production called the
nucleolus:
12
Karyotype
•
•
•
An ordered, visual representation of the chromosomes in a cell
Chromosomes are photographed when they are highly condensed, then photos
of the individual chromosomes are arranged in order of decreasing size:
In humans each somatic cell has 46 chromosomes, made up of two sets, one
set of chromosomes comes from each parent
Pair of homologous
chromosomes
5 µm
Centromere
Sister
chromatids
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Chromosomes
•
•
•
Non-homologous chromosomes
– Look different
– Control different traits
Sex chromosomes
– Are distinct from each other in their
characteristics
– Are represented as X and Y
– Determine the sex of the individual, XX being
female, XY being male
In a diploid cell, the chromosomes occur in pairs.
The 2 members of each pair are called
homologous chromosomes or homologues.
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Chromosomes
•
•
•
A diploid cell has two sets of each of its chromosomes
A human has 46 chromosomes (2n = 46)
In a cell in which DNA synthesis has occurred all the chromosomes are
duplicated and thus each consists of two identical sister chromatids
Maternal set of
chromosomes (n = 3)
2n = 6
Paternal set of
chromosomes (n = 3)
Two sister chromatids
of one replicated
chromosome
Centromere
Two nonsister
chromatids in
a homologous pair
Pair of homologous
chromosomes
(one from each set)
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Homologues
• Homologous chromosomes:
• Look the same
• Control the same traits
• May code for different forms of each trait
• Independent origin - each one was inherited
from a different parent
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Genes
•
•
•
Gene – a section of a DNA molecule that contains
the code for making one polypeptide.
Gene locus –the location of a gene along the
length of a chromosome
Alleles – genes that can occupy the same gene
locus (on different chromosomes)
Red eyes
White eyes
Short wings
Long wings
Tan body
Tan body
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Homologues
•
However, homologous chromosomes are not
identical because they may code for different forms
of each trait:
Red eyes
Short wings
Tan body
White eyes
Long wings
Tan body
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Chromosome Duplication
•
•
In preparation for cell division, DNA is replicated and the chromosomes condense
Each duplicated chromosome has two sister chromatids, which separate during cell
division
0.5 µm
A eukaryotic cell has multiple
chromosomes, one of which is
represented here. Before
duplication, each chromosome
has a single DNA molecule.
Once duplicated, a chromosome
consists of two sister chromatids
connected at the centromere. Each
chromatid contains a copy of the
DNA molecule.
Mechanical processes separate
the sister chromatids into two
chromosomes and distribute
them to two daughter cells.
Chromosome
duplication
(including DNA
synthesis)
Centromere
Separation
of sister
chromatids
Sister
chromatids
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Centrometers
Sister chromatids
Chromosome Duplication
•
•
Because of duplication, each condensed chromosome
consists of 2 identical chromatids joined by a centromere.
Each duplicated chromosome contains 2 identical DNA
molecules (unless a mutation occurred), one in each
chromatid:
Non-sister
chromatids
Centromere
Duplication
Sister
chromatids
Two unduplicated
chromosomes
Sister
chromatids
Two duplicated chromosomes
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20
Structure of Chromosomes
•
•
The centromere is a constricted region of the chromosome containing a
specific DNA sequence, to which is bound 2 discs of protein called
kinetochores.
Kinetochores serve as points of attachment for microtubules that move
the chromosomes during cell division:
Metaphase chromosome
Centromere
region of
chromosome
Kinetochore
Kinetochore
microtubules
Sister Chromatids
21
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Structure of Chromosomes
–
–
Diploid - A cell possessing two copies of each chromosome
(human body cells).
 Homologous chromosomes are made up of sister
chromatids joined at the centromere.
Haploid - A cell possessing a single copy of each
chromosome (human sex cells).
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Phases of the Cell Cycle
•
•
•
Interphase
–
G1 - primary growth
–
S - genome replicated
–
G2 - secondary growth
M - mitosis
C - cytokinesis
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Interphase
•
•
G1 - Cells undergo majority of growth
S - Each chromosome replicates (Synthesizes) to
produce sister chromatids
– Attached at centromere
– Contains attachment site (kinetochore)
•
G2 - Chromosomes condense - Assemble
machinery for division such as centrioles
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Mitosis



Some haploid & diploid cells divide by mitosis.
Each new cell receives one copy of every
chromosome that was present in the original cell.
Produces 2 new cells that are both genetically
identical to the original cell.
DNA duplication
during interphase
Mitosis
Diploid Cell
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Mitotic Division of an Animal Cell
G2 OF INTERPHASE
Centrosomes
(with centriole pairs)
Nucleolus
Chromatin
(duplicated)
Nuclear
Plasma
envelope membrane
PROPHASE
Early mitotic
spindle
Aster
Centromere
Chromosome, consisting
of two sister chromatids
PROMETAPHASE
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
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Mitotic Division of an Animal Cell
METAPHASE
ANAPHASE
Metaphase
plate
Spindle
Centrosome at Daughter
one spindle pole chromosomes
TELOPHASE AND CYTOKINESIS
Cleavage
furrow
Nucleolus
forming
Nuclear
envelope
forming
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G2 of Interphase
• A nuclear envelope bounds
the nucleus.
• The nucleus contains one or
more nucleoli (singular,
nucleolus).
• Two centrosomes have
formed by replication of a
single centrosome.
• In animal cells, each
centrosome features two
centrioles.
• Chromosomes, duplicated
during S phase, cannot be
seen individually because
they have not yet condensed.
G2 OF INTERPHASE
Centrosomes
(with centriole pairs)
Chromatin
(duplicated)
The light micrographs show dividing lung cells
from a newt, which has 22 chromosomes in its
somatic cells (chromosomes appear blue,
microtubules green, intermediate filaments
red). For simplicity, the drawings show only
four chromosomes.
Nucleolus
Nuclear
Plasma
envelope membrane
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Prophase
• The chromatin fibers become
more tightly coiled, condensing
into discrete chromosomes
observable with a light
microscope.
• The nucleoli disappear.
• Each duplicated chromosome
appears as two identical sister
chromatids joined together.
• The mitotic spindle begins to form.
It is composed of the centrosomes
and the microtubules that extend
from them. The radial arrays of
shorter microtubules that extend
from the centrosomes are called
asters (“stars”).
• The centrosomes move away from
each other, apparently propelled
by the lengthening microtubules
between them.
PROPHASE
Early mitotic
spindle
Aster
Centromere
Chromosome, consisting
of two sister chromatids
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Metaphase
• Metaphase is the longest stage of
mitosis, lasting about 20 minutes.
• The centrosomes are now at
opposite ends of the cell.
•The chromosomes convene on the
metaphase plate, an imaginary
plane that is equidistant between
the spindle’s two poles. The
chromosomes’ centromeres lie on
the metaphase plate.
• For each chromosome, the
kinetochores of the sister
chromatids are attached to
kinetochore microtubules coming
from opposite poles.
• The entire apparatus of
microtubules is called the spindle
because of its shape.
METAPHASE
Metaphase
plate
Spindle
Centrosome at
one spindle pole
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The Mitotic Spindle
•
•
•
•
•
The spindle includes the centrosomes, the spindle
microtubules, and the asters
The apparatus of microtubules controls
chromosome movement during mitosis
The centrosome replicates, forming two
centrosomes that migrate to opposite ends of the
cell
Assembly of spindle microtubules begins in the
centrosome, the microtubule organizing center
An aster (a radial array of short microtubules)
extends from each centrosome
31
The Mitotic Spindle
•
Some spindle microtubules attach to the
kinetochores of chromosomes and move the
chromosomes to the metaphase plate
Aster
Microtubules
Sister
chromatids
Chromosomes
Centrosome
Metaphase
plate
Kinetochores
Centrosome
1 µm
Overlapping
nonkinetochore
microtubules
Kinetochore
microtubules
0.5 µm
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The Mitotic Spindle
•
•
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
Chromosome
movement
Microtubule
Motor
protein
Kinetochore
Tubulin
subunits
Chromosome
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Anaphase
• Anaphase is the shortest stage of
mitosis, lasting only a few minutes.
• Anaphase begins when the two sister
chromatids of each pair suddenly part.
Each chromatid thus becomes a fullfledged chromosome.
• The two liberated chromosomes begin
moving toward opposite ends of the cell,
as their kinetochore microtubules
shorten. Because these microtubules are
attached at the centromere region, the
chromosomes move centromere first (at
about 1 µm/min).
• The cell elongates as the
nonkinetochore microtubules lengthen.
• By the end of anaphase, the two ends of
the cell have equivalent—and
complete—collections of chromosomes.
ANAPHASE
Daughter
chromosomes
34
Telophase
• Two daughter nuclei begin to
form in the cell.
• Nuclear envelopes arise from
the fragments of the parent
cell’s nuclear envelope and
other portions of the
endomembrane system.
• The chromosomes become
less condensed.
• Mitosis, the division of one
nucleus into two genetically
identical nuclei, is now
complete.
TELOPHASE AND CYTOKINESIS
Cleavage
furrow
Nucleolus
forming
Nuclear
envelope
forming
35
Mitosis in a plant cell
Chromatine
Nucleus
Nucleolus condensing
1 Prophase.
The chromatin
is condensing.
The nucleolus is
beginning to
disappear.
Although not
yet visible
in the micrograph,
the mitotic spindle is
staring to from.
Chromosome
Metaphase. The
2 Prometaphase.
3
4
spindle is complete,
We now see discrete
and the chromosomes,
chromosomes; each
attached to microtubules
consists of two
at their kinetochores,
identical sister
are all at the metaphase
chromatids. Later
plate.
in prometaphase, the
nuclear envelop will
fragment.
5
Anaphase. The
chromatids of each
chromosome have
separated, and the
daughter chromosomes
are moving to the ends
of cell as their
kinetochore
microtubles shorten.
Telophase. Daughter
nuclei are forming.
Meanwhile, cytokinesis
has started: The cell
plate, which will
divided the cytoplasm
in two, is growing
toward the perimeter
of the parent cell.
36
Cytokinesis
•
Cleavage of cell into two
halves
– Animal cells
 Constriction belt of
actin filaments
– Plant cells
 Cell plate
– Fungi and protists
 Mitosis occurs
within the nucleus
37
Cytokinesis In Animal And Plant Cells
100 µm
Cleavage furrow
Contractile ring of
microfilaments
Vesicles
forming
cell plate
Wall of
patent cell
1 µm
Cell plate
New cell wall
Daughter cells
Daughter cells
(a) Cleavage of an animal cell (SEM)
(b) Cell plate formation in a plant cell (SEM)
38
39
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
Cell wall
Origin of
replication
Plasma
membrane
E. coli cell
Chromosome
replication begins.
Soon thereafter,
one copy of the origin
moves rapidly toward
the other end of the cell.
Replication continues.
One copy of the origin
is now at each end of
the cell.
Bacterial
chromosome
Two copies
of origin
Origin
Origin
Replication finishes.
The plasma membrane
grows inward, and
new cell wall is
deposited.
Two daughter
cells result.
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Prokaryote Cell Division - Binary Fission
•
•
•
•
Replication begins at a specific site called the origin of replication and
proceeds bidirectionally in a circle
Cell elongates and the newly replicated DNA molecules are actively
partitioned.
The cytoplasm is divided by growth of a new membrane and septum.
Produces 2 daughter cells which are genetically identical (unless a
mutation occurred) to each other and to the original cell.
Origin of replication
Prokaryotic
genome
Replication
of DNA
Elongation of cell and
partitioning of DNA
Formation of new membrane
and septum
Inward growth of septum
Cell pinches in two
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
41
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
Bacterial
chromosome
Prokaryotes
Chromosomes
Microtubules
Dinoflagellates
Intact nuclear
envelope
Kinetochore
microtubules
Intact nuclear
envelope
Diatoms
Kinetochore
microtubules
Centrosome
Most eukaryotes
Fragments of
nuclear envelope
42
Cell Cycle Control System
•
•
•
•
The 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
Cell can be put on hold at specific
checkpoints.
43
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 clock has specific checkpoints where the cell cycle stops until a goahead signal is received
G1 checkpoint
Control
system
S
G1
M
G2
M checkpoint
Figure 12.14
G2 checkpoint
44
G1 checkpoint
G0
G1 checkpoint
G1
(a) If a cell receives a go-ahead signal at
the G1 checkpoint, the cell continues
on in the cell cycle.
G1
(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.
45
“Go Ahead Signals” - Regulatory Proteins - Cyclins
•
•
•
•
To pass each checkpoint, specific regulatory proteins called cyclins must
bind to an enzyme called Cyclin-dependent kinase (Cdk).
They are synthesized during the stage preceding that checkpoint
The cyclin-Cdk complex then activates numerous proteins needed for
the next stage of the cell cycle by phosphorylating them
The cyclins are then quickly degraded during the stage following that
checkpoint
P
Cyclin
Cyclin-dependent kinase
(Cdk)
P
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
46
(a) Fluctuation of MPF activity and
cyclin concentration during
the cell cycle
Relative Concentration
Molecular control at the G2 checkpoint
M-Phase Promoting Factor - MPF
G1 S G2 M
MPF activity
G 1 S G2 M
Cyclin
Time
(b) Molecular mechanisms that
help regulate the cell cycle
1 Synthesis of cyclin begins in late S
phase and continues through G2.
Because cyclin is protected from
degradation during this stage, it
accumulates.
5 During G1, conditions in
the cell favor degradation
of cyclin, and the Cdk
component of MPF is
recycled.
Cdk
Degraded
Cyclin
Cyclin is
degraded
4 During anaphase, the cyclin component
of MPF is degraded, terminating the M
phase. The cell enters the G1 phase.
G2
Cdk
checkpoint
MPF
Cyclin
2 Accumulated cyclin molecules
combine with recycled Cdk molecules, producing enough molecules
of MPF to pass the G2 checkpoint and
initiate the events of mitosis.
3 MPF promotes mitosis by phosphorylating
various proteins. MPF‘s activity peaks during
metaphase.
47
Stop and Go Signs: Internal and External
Signals at the Checkpoints
•
•
Internal - Cyclins and Cyclin-dependent kinases
(Cdks)
An example of an internal signal is that
kinetochores not attached to spindle microtubules
send a molecular signal to delays anaphase
48
Stop and Go Signs: Internal and External
Signals at the Checkpoints
•
•
Some external signals are growth factors, proteins
released by certain cells that stimulate other cells
to divide
Growth Factors stimulate other cells to divide
–
–
–
In multicellular organisms, passage through cell cycle
check points is stimulated by growth factors
Over 50 different growth factors have been identified,
and each one binds to a different cell surface receptor
Each growing cell binds with growth factors that
stimulate cell division
49
Growth Factors and the Cell Cycle
•
•
When a growth factor binds to the cell surface
receptor, this triggers an intracellular signaling
cascade that activates regulatory proteins inside
the nucleus.
The activated nuclear regulatory proteins stimulate
DNA to produce proteins (e.g. Cdk or cyclins)
needed to pass through cell cycle checkpoints
50
External Growth Factors
•
•
•
For example, platelet-derived growth factor
(PDGF) stimulates the division of human
fibroblast cells in culture
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
51
Cancer
•
•
•
•
Loss of Cell Cycle Controls
Cancer cells do not respond normally to the body’s control mechanisms
They exhibit neither density-dependent inhibition nor anchorage
dependence
Form tumors
Lymph
vessel
Tumor
Glandular
tissue
1 A tumor grows from a
single cancer cell.
2 Cancer cells invade
neighboring tissue.
Blood
vessel
Cancer cell
3 Cancer cells spread
through lymph and
blood vessels to
other parts of the body.
Metastatic
Tumor
4 A small percentage of
cancer cells may survive
and establish a new tumor
in another part of the body.
52