Download Mitosis and the Cell Cycle 10/21/05 Lecture Outline Phases of the

Mitosis and the Cell Cycle
10/21/05
Lecture Outline
• Two goals of the Cell Cycle:
– Make one cell into two
– Must accurately replicate the genetic material
• Mitosis (replicate and distribute the
chromosomes)
– Major phases
– Mechanics of chromosome segregation
• Cytokinesis (how does one cell become two?)
• Replication of the cytoplasm and organelles
• Control of the Cell Cycle
1
Phases of the Cell Cycle
– The mitotic phase (M)
– Interphase
• Genetic information is copied exactly
into each daughter cell
INTERPHASE
C
M yto
ito ki
si ne
s si
s
G1
2
Mitosis and the Cell Cycle
• The cell cycle consists of
• G1
• S
• G2
– Cyclins and CDKs
– The importance of checkpoints for quality control
S
(DNA synthesis)
• See it in action
G2
MI
(M T O T
) P IC
HA
SE
Figure 12.5
3
4
1
• Each duplicated chromosome
Overview of Mitosis
Has two sister chromatids, which separate
during cell division
0.5 µm
One chromosome, one DNA molecule
G2 OF
INTERPHASE
Centrosomes
Chromatin
(with centriole pairs)
(duplicated)
Duplication
PROPHASE
Early mitotic
spindle
Aster
Centromere
PROMETAPHASE
Fragments
Kinetochore
of nuclear
envelope
Nonkinetochore
microtubules
Centromere
One chromosome, two DNA molecules
(Two attached chromatids)
Sister
chromatids
Figure 12.6
Sister chromosomes separate
during mitosis
Centromeres
Sister chromatids
5
ANAPHASE
Figure 12.6
Spindle
Centrosome at Daughter
one spindle pole chromosomes
Metaphase:
Chromosomes align in
center of cell
Chromosome, consisting
of two sister chromatids
Kinetochore
microtubule
Balanced attachment of spindle fibers to both chromatids
aligns chromosomes in metaphase
Overview of Mitosis
Metaphase
plate
Prometaphase:
Nuclear envelope
breaks down.
Chromosomes
Prophase:
attach to spindle
Chromosomes begin to condense.
6
Spindle starts to form
Nuclear
Plasma
envelope membrane
DNA replication during
Interphase
Figure 12.4
METAPHASE
Nucleolus
TELOPHASE AND CYTOKINESIS
Cleavage
furrow
Nuclear
envelope
forming
Anaphase:
Sister chromatids separate
Nucleolus
forming
Telophase:
Complete
set of
chromosom
es at each
pole
7
“tug of war”
8
2
Kinetochore microtubules
attach to centromeres
and direct the poleward
movement of
chromosomes
Nonkinetechore
microtubules from opposite
poles overlap and push
Both chromatids must be captured by
spindle fibers. If any kinetochores
remain unattached, chromosomes will
not separate
Aster
Sister
chromatids
Spindle fibers shorten at the kinetochore
Centrosome
Mark
Metaphase
Plate
Kinetochores
Overlapping
nonkinetochore
microtubules
Kinetochores
microtubules
Microtubules
0.5 µm
Chromosomes
against each other, elongating
the cell
Figure 12.7
Centrosome
1 µm
9
Cytokinesis
Kinetochore
Chromosome
movement
10
Animal cells divide by
constriction
Kinetochore
Cleavage furrow
Microtubule
100 µm
Tubulin
subunits
Motor
protein
Plant cells build a
partition (cell plate)
Chromosome
Contractile ring of
microfilaments
11
Figure 12.9 A
Daughter cells
(a) Cleavage of an animal cell (SEM)
Vesicles Wall of
1 µm
forming patent cellCell plate
New cell wall
cell plate
Daughter cells
(b) Cell
Figure 12.9
B plate formation in a plant cell
12 (SEM)
3
How do the cytoplasmic
organelles divide?
Phases of the Cell Cycle
• The cell cycle consists of
– The mitotic phase (M)
– Interphase
• Mitochondria (and chloroplasts) are
present in multiple copies, and
randomly segregate into the two
daughter cells.
• G1
• S
• G2
INTERPHASE
S
(DNA synthesis)
C
M yto
ito ki
si ne
s si
s
G1
• Membrane bound organelles (e.g.
ER) fragment along with the nuclear
membrane and are reconstructed in
the daughter cells
13
The clock has specific checkpoints: the cell cycle
Figure 12.5
14
Cell Cycle Control System
stops until a go-ahead signal is received
See cell-cycle game at:
http://nobelprize.org/medicine/educational/2001/cellcycle.html
•S-PHASE ENTRY (G1/S)
–Mitosis Complete?
–Growth/ Protein
Synthesis adequate?
–No DNA Damage?
•MITOSIS EXIT:
–All chromosomes
attached to
spindles?
G 1 checkpoint
Control
system
Figure 12.15 A, B
(a) If a cell receives a go-ahead signal at
the G 1 checkpoint, the cell continues
on in the cell cycle.
G1
15
•MITOSIS ENTRY (G2/M)
–Replication Complete?
–Growth/ Protein Synthesis
adequate?
–No DNA Damage?
S
G1
G0
G1 checkpoint
G1
G2
MI
(M T O T
) P IC
HA
SE
M
G2
Figure 12.14
16
(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.
4
Phosphorylation of CDK Targets Changes Their Activity
The Cell Cycle Clock:
Cyclins and Cyclin-dependent kinases
Cyclins
Cyclin levels in the cell rise and fall
with the stages of the cell cycle.
– G1 cyclin (cyclin D)
– S-phase cyclins (cyclins E and A)
– M-phase cyclins (cyclins B and A)
Cyclin-dependent kinases (Cdks)
– G1 Cdk (Cdk4)
– S-phase Cdk ((Cdk2)
– M-phase Cdk (Cdk1)
Cdk levels remain stable, but each
must bind the appropriate cyclin
(whose levels fluctuate) in order to be
activated.
Now performs
a cell cycle function
17
18
How does the cell cycle cycle?
The Human Cell Cycle
Focus first on entry
and exit from
mitosis
~ 1 hour
~ 4 hours
~ 10 hours
~ 9 hours
19
20
5
The Cell Cycle According to Cyclin Abundance
Cyclin-CDK controls
the cell cycle
Cyclin B synthesized in S phase;
Combines with cdk1 to make active
MPF
Cyclin component degraded
in anaphase
MPF triggers:
–assembly of the mitotic spindle
–breakdown of the nuclear envelope
–condensation of the chromosomes
Cyiclin-CDK activity can also be
controlled by inhibitors22
21
How are CDKs Regulated?
CDKs are Regulated
by Phosphorylation
is a kinase
Isolate mutants that divide too early or too late
23
is a phosphatase
CAK
(CDK
Activating
Kinase)
24
6
Cyclin Dependent Kinase Inhibitors (CKIs)
Conformational Changes Associated
with CDK Phosphorylation
Free CDK
CDK + Cyclin
T161 phosphorylation
p21
CDK
CDK
Cyclin
Cyclin
p21
p16
CDK4
CDK4
p16
Cyclin
The T-loop blocks
substrate access
Binding of cyclin
moves the T-loop
Phosporylation moves
25
the T-loop more
Cell Cycle Regulators and
Cancer
26
Anaphase promoting complex
Triggers:
Chromosome separation
Breakdown of cyclin to re-start the cycle
Breakdown of geminin Cdc20
(to again allow replication)
E2-Ub
Cdh1
APC
Cyclin-Cdk
G2
27
Metaphase
Securin
Cyclin-Cdk
Anaphase
G1
28
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Prophase
Metaphase
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MCB Fig. 13-19
Prometaphase
Anaphase
Telophase
30
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