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Cell cycle

The cell cycle: cells duplicate their


contents and divide

The cell cycle may be divided


into 4 phases

The cell cycle triggers essential


processes
(DNA replication, mitosis)

Progression of the cell cycle is regulated


by feedback from intracellular events

Chemical Signals tell a cell


when to start and stop dividing.

Checkpoint control system


Checkpoints
cell cycle controlled by STOP & GO
chemical signals at critical points
signals indicate if key cellular
processes have been
completed correctly

Checkpoint control system


3 major checkpoints:
G1/S

can DNA synthesis begin?

G2/M

has DNA synthesis been


completed correctly?
commitment to mitosis

spindle checkpoint
are all chromosomes
attached to spindle?
can sister chromatids
separate correctly?

G1/S checkpoint
G1/S checkpoint is most critical
primary decision point
restriction point it has two cases

GO signal if cell receives signal


, it divides two types of signals
internal signals: cell growth (size),
cell nutrition
external signals: growth factors

No signal if cell does not


receive signal, it exits cycle &
switches to G0 phase
non-dividing, working state

G0 Phase

G1 PHASE

Problems
resolved, reenter S phase

S PHASE

The cell cycle stops between G1 and S


phase for checks to be made.

Any problems, the cycle enters G0 phase


while the problem is sorted

G0 phase

G0 phase

non-dividing, differentiated state


most human cells in G0 phase
liver cells

M
Mitosis
G2
Gap 2

S
Synthesis

in G0, but can be

G1
Gap 1

called back to cell


cycle by external cues
nerve & muscle cells
G0
highly specialized;
Resting
arrested in G0 & can
never divide

HALT!!!!! There has been a


problem with the DNA
transcription.I can not give you
a pass (Cdk), you must wait
here till the DNA is fixed!!!!
G2 PHASE

M PHASE

STOP!!!!
Is your DNA
replication complete?
Is your DNA intact??
G2 PHASE

M PHASE

If the DNA replication


is complete and intact
the cell can continue
through the cycle.

Checkpoint Problems
If checkpoints come across a problem
E.g.: DNA Damage
Produce Cdk inhibitor protein
Block/stop Cdk signals
No passes are given out so there is no progression
Cell does not move to next phase until repair is
complete

Go-ahead signals
1-Protein signals that promote cell growth &
division
A. internal signals
promoting factors
B. external signals
growth factors
2-Primary mechanism of control
phosphorylation
kinase enzymes
either activates or inactivates cell signals

Cell cycle signals

inactivated Cdk

Cell cycle controled by


a) cyclins
regulatory proteins
levels cycle in the cell
b) Cdks
activated Cdk
cyclin-dependent kinases
phosphorylates cellular proteins
activates or inactivates proteins
c) Cdk-cyclin complex
triggers passage through different stages
of cell cycle

Cyclin & Cyclin-dependent kinases proteins


CDKs & cyclin drive cell from one phase to next
in cell cycle

Proper regulation of cell cycle is so key to life


that the genes for these regulatory proteins have
been highly conserved through evolution

The genes are basically the same in yeast,


insects, plants & animals (including humans)

Cyclin & Cyclin-dependent kinases proteins

CDK and cyclin together form an


enzyme that activates other proteins
by chemical modification
(phosphorylation).
The amount of CDK molecules is
constant during the cell cycle, but
their activities vary because of the
regulatory function of the cyclins.

Cyclin and cyclin dependent kinases


map during cell cycle
Cyclin D-CDK4

Cyclin E-CDK2

CDK
inhibitors

Cyclin B-CDC2

Cyclin A-CDK2

Cancer how does it


happen
Cancer is essentially a failure of cell division control
unrestrained, uncontrolled cell growth
What control is lost?
lose checkpoint stops
gene p53 plays a key role in G1/S restriction point
p53 protein halts cell division if it detects damaged
DNA
p53 is the options:
Cell Cycle
stimulates repair enzymes to fix DNA
Enforcer
forces cell into G0 resting stage
keeps cell in G1 arrest
causes apoptosis of damaged cell
ALL cancers have to shut down p53 activity

Cancer
Tumor: abnormal mass of tissue that results
from lack of balance in cell division and
apoptosis
Benign: usually slow growing and harmless
Malignant: invades adjacent tissue, more likely to
metastasize

Cancer cells are no longer under cell cycle


control, daughter cells free of control, too

p53 master regulator gene


(normal cell)
NORMAL p53
p53 allows cells
with repaired
DNA to divide.

p53
protein

DNA repair enzyme

p53
protein

Step 1

Step 2

Step 3

DNA damage is caused


by heat, radiation, or
chemicals.

Cell division stops, and


p53 triggers enzymes to
repair damaged region.

p53 triggers the destruction


of cells damaged beyond repair.

p53 master regulator gene


(Cancer cell)
ABNORMAL p53

abnormal
p53 protein

Step 1

Step 2

DNA damage is
caused by heat,
radiation, or
chemicals.

The p53 protein fails to stop


cell division and repair DNA.
Cell divides without repair to
damaged DNA.

cancer
cell

Step 3
Damaged cells continue to divide.
If other damage accumulates, the
cell can turn cancerous.

Development of Cancer

Cancer develops only after a cell experiences ~6


key mutations (hits)
unlimited growth
turn on growth promoter genes
ignore checkpoints
turn off tumor suppressor genes (p53)
escape apoptosis
Its like an
turn off suicide genes
out of contro
immortality = unlimited divisions
car!
turn on chromosome maintenance genes
promotes blood vessel growth
turn on blood vessel growth genes
overcome anchor & density dependence
turn off touch-sensor gene