Cell Cycle

• Who has a bigger cell? Elephant or

Mouse?
• Why do cells divide instead of just growing
bigger?
– The larger the cell, the more demands it
places on DNA
• Small cells, the DNA can meet the needs of the
cell
• As cell grows, the DNA can not meet the needs of
the cell – does not make extra copies of DNA to
meet needs
 Cell Size
• The larger the cell, the more difficult it is to
transport nutrients and waste across the
cell membrane. The cell membrane’s
inefficiency increases
– Exchange rate of materials is dependent on
the surface area
• S.A. = Length X Width X # of sides
– The rate of materials used and waste
produced is dependent on volume
• Volume = Length X Width X Height
• Understanding the relationship between
surface area to volume is the key to
understanding why cells must divide as
they grow
 The Cell Cycle (Movie)
• Normal growth, development, and
maintenance depend on the timing and
rate of mitosis (cell division). Various cells
differ in their pattern of cell division:
• Human skin cells  frequent
• Liver cells  only in appropriate situations
• Nerve cells  do not divide in mature
humans
 Frequency of cell division
 Frequency of cell division varies by cell type
 embryo
 cell cycle < 20 minute
 skin cells
 divide frequently throughout life
 12-24 hours cycle
 liver cells
 retain ability to divide, but keep it in reserve M
 divide once every year or two metaphase anaphase
prophase telophase
 mature nerve cells & muscle cells G2
C

 do not divide at all after maturity

interphase (G1, S, G2 phases)
 permanently in G0 mitosis (M)
cytokinesis (C) G
S 1

AP Biology
Fig. 12-5

S
G1 (DNA synthesis)

sis
e
kins
G2
to
si

y
ito

MITC
M

(M) OTIC
PHA
SE
 Checkpoints
• The cell cycle is regulated by a molecular
signaling system which switches the cell
cycle control system on/off.
• The system consists of a molecular clock
and checkpoints to ensure conditions are
met before moving on to the next steps.
• Malfunctions may lead to cancer.
 There’s no
turning back,

Overview of Cell Cycle Control now!

 Two irreversible points in cell cycle

 replication of genetic material
 separation of sister chromatids

 Checkpoints
 process is assessed & possibly halted
sister chromatids

centromere  
single-stranded double-stranded
AP Biology
chromosomes chromosomes
Fig. 12-14
G1 checkpoint

Control
system S
G1

M G2

M checkpoint
G2 checkpoint
 Cycle Phases
• G1 – First growth phase. Metabolic activity
proceeds at a normal rate. Duration highly
variable. Synthesis of enzymes related to DNA
replication.
• G0 – Quiescent (rest) state. Usually for non-
proliferative cells. Can occur for cells that are
damaged. Alternative to apoptosis. Can be
temporary or permanent.
• Nerve and muscle cells (multinucleated)
• S – DNA replication.
– All chromosomes replicated.
– Chromosomes consist of 2 sister chromatids in
chromatin form.

Chromosome
• 1 long string of DNA Sister
chromatids
• Loose- chromatin
• Tight - chromatid
Fig. 12-4
0.5 µm Chromosomes DNA molecules

Chromo-
Chromosome
some arm
duplication
(including DNA
synthesis)
Centromere

Sister
chromatids

Separation of
sister chromatids

Centromere

Sister chromatids
• G2
– Second growth phase.
– Reproduction of some organelles. High microtubule
production.
– Two centrosomes. Aster around each centrosome.
Cells grow in size.
• M – Mitosis.
– Prophase, Prometaphase, Metaphase, Anaphase,
Telophase
• Cytokinesis
– Birth of 2 daughter cells
Fig. 12-7 Aster
Centrosome
Sister
chromatids
Microtubules Chromosomes
Metaphase
plate

Kineto-
chores

Centrosome 1 µm

Overlapping
nonkinetochore Kinetochore
microtubules microtubules

0.5 µm
 Internal and External Signals for
Mitosis
• Growth Factors
• Density-dependent inhibition
– Crowded cells stop dividing
• Anchorage dependence
– Must be attached to …
• ECM or culture of a jar
 The Cell Cycle Clock/Checkpoints
2 Types of Regulatory Molecules, together act as a
checkpoint
1) Kinases
– Amount doesn’t fluctuate
– enzymes that phosphorylates molecules
– Cyclin dependent kinase (Cdk) – inactive (G1 & G2) until cyclin
are present
2) Cyclins
– Molecule concentration fluctuates (unlike kinase)
– Bonds w/ Kinase and serves a checkpoint
– Cyclin-Cdk complex (MPF M-phase promoting factor) promotes
certain activities that eventually lead to the next stage of the cell
cycle
– Having the minimum concentration of these complexes help the
cell cycle proceed through the checkpoints
 Actual Checkpoints
• Click on normal cell division (top left)
 Steps of the Cell Cycle
• Sometime after cytokinesis G1 cyclins rise and
bind to their Cdks (activates Cdks) which
signals the cell to prepare for chromosome
replication.– This moves cell past G1
checkpoint
• “S” phase promoting factor (SPF) enters the
nucleus, prepares the cell to duplicate its DNA
and centrosomes – S phase begins -
• S-cyclin-Cdk complexes form. They
phosphorylate proteins that ensure DNA
replication.
Fig. 12-17
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

Cyclin accumulation
G1
Cdk

M
Degraded G2
cyclin
G2 Cdk
Cyclin is checkpoint
degraded

Cyclin
MPF

(b) Molecular mechanisms that help regulate the cell cycle

 In depth Animation
• During G2, M-phase cyclins begin to rise and form
Mitosis promoting factors (MPF) (M cyclin Cdk
complexes).
• G2 checkpoint: Checks for DNA damage.
• Then MPF initiates assembly of mitotic spindle, the
breakdown of the nuclear envelope, cessation of gene
transcription, and condensation of the chromosomes,
and taking the cell cycle all the way to metaphase.
• M checkpoint: All chromosomes are aligned at the
metaphase plate,
• MPF activates the Anaphase Promoting Complex (APC)
which allows sister chromatids to separate which
activates G1 cyclins, and degrades M cyclins.
 Quality Control
• Systems for interrupting the cell cycle if something
goes wrong
1) DNA damage checkpoint
1) happens at G1 checkpoint + S phase + M phase
2) P53 gene – tumor suppresor
2) Completion of S-phase
1) Makes sure that there are no okazaki fragments (short
sequences of DNA wcreate the lagging strand during
DNA replication..
3) Spindle Checkpoint
1) Assures spindles are properly connected to kinetichore
• If problem cannot be fixed, the cell signals for
apoptosis - Movie
 Cancer
• A group of diseases that involve irregular growth
and reproduction of cells
• Cancer occurs when genes involved in the
cycle, specifically with check points are altered
(growth factors)
• Transformation – single cell converts to a cancer
cell
• Benign Tumor – a group of abnormal cells that
does not invade other body systems- not
considered cancerous
• Metastasis – when cancerous cells break off the
original tumor and travel to other parts of the body
• Malignant Tumor – a tumor that invades a body
system by traveling via the bloodstream or the
lymphatic system
• Cancer causes death b/c the cells take over the
function of organs
• Cancer arises due to damage to genes (90%) or
inheritance (10)
 Fig. 12-20

Lymph
vessel
Tumor
Blood
vessel

Cancer
Glandular
cell
tissue Metastatic
tumor
1 A tumor grows 2 Cancer cells 3 Cancer cells spread 4 Cancer cells may
from a single invade neigh- to other parts of survive and
cancer cell. boring tissue. the body. establish a new
tumor in another
part of the body.
 Growth Factors and Cancer
 Growth factors can create cancers
 proto-oncogenes
 normally activates cell division
 growth factor genes
 become Oncogenes (cancer-causing) when mutated
 if switched “ON” can cause cancer
 example: RAS (activates cyclins)
 Tumor Suppressor Genes
 normally inhibits cell division
 if switched “OFF” can cause cancer. Why?
 example: p53
AP Biology
 Cancer & Cell Growth
 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 G resting stage

0
 keeps cell in G arrest
1
 causes apoptosis of damaged cell

 ALL cancers have to shut down p53 activity

 Inhibits blood vessel growth in tumors (angiogenesis)

AP Biology p53 discovered at Stony Brook by Dr. Arnold Levine

 p53 — master regulator gene
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 Cell division stops, and p53 triggers the destruction
by heat, radiation, or p53 triggers enzymes to of cells damaged beyond
chemicals. repair damaged region. repair.

ABNORMAL p53

abnormal
p53 protein

cancer
Step 1 Step 2 cell
DNA damage is The p53 protein fails to stop Step 3
caused by heat, cell division and repair DNA. Damaged cells continue to divide.
radiation, or Cell divides without repair to If other damage accumulates, the
damaged DNA.
AP chemicals.
Biology 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
 turn off suicide genes It’s like an
out-of-control
 immortality = unlimited divisions car with many
 turn on chromosome maintenance genes systems failing!
 promotes blood vessel growth
 turn on blood vessel growth genes
 overcome anchor & density dependence
 turn off touch-sensor gene
AP Biology
 What causes these “hits”?
 Mutations in cells can be triggered by
 UV radiation  cigarette smoke
 chemical exposure  pollution
 radiation exposure  age
 heat  genetics

AP Biology
 Tumors
 Mass of abnormal cells
 Benign tumor
 abnormal cells remain at original site as a
lump
 p53 has halted cell divisions
 most do not cause serious problems &
can be removed by surgery
 Malignant tumor
 cells leave original site
 lose attachment to nearby cells
 carried by blood & lymph system to other tissues
 start more tumors = metastasis
 impair functions of organs throughout body
AP Biology
 Mitosis
• Mitosis – reproduction of the nucleus
• Cytokinesis – division of the cytoplasm
• Diploid (2n) – cells that have 2 sets of
chromosomes (46)
• Haploid (n) - cells that have 1 set of
chromosomes (23)
• Somatic cells – cells that only undergo
mitosis
 Diploid – 2n
• M1 + D1 are homologous
• Zygote = egg + sperm

m1 m2 m3 D1 D2 D3

• Allele: different versions of the same trait

• During G2 -Tetraploid – 4n

m1 m1 D1 D1

46 – double stranded chromosomes

• Egg and Sperm produced in Meiosis

(haploid)

Egg (n) Sperm (n)

+
 Stage
• G1 – Diploid (2n)
• S – Tetraploid (4n) Interphase
• G2 – Tetraploid
• Mitosis…
Prophase-
-Chromatin fibers begin to condense into
chromosomes and wind around histone
proteins.
-Nucleoli disappears.
-Chromosomes become visible. Chromatid
arms held together by cohesions
(vertebrates only at the centromere).
-Mitotic spindle forms, extending from the
centrosomes outside the nucleus forming
asters. Centrioles (found in animal and
lower plant cells) are in the center of the
centrosome.
-The centrosomes are moving to opposite
poles.
Prometaphase
-The nuclear envelopes fragments and
nucleolus is not longer visible.
-Centrosomes are at opposite ends of the
nuclear area.
-The microtubules extend through the
nuclear area
-2 Kinetochores (facing opposite from one
another) form on the centromere. These are
protein structures that allow microtubules to
attach.
-Kinetochore microtubules attach to the
kinetochores. Moving the chromosomes back
and forth until they reach the middle of the
cell.
Metaphase-
-Longest phase of mitosis.
-The “tug and pull” of the kinetochore
microtubules brings the twin chromatids
to the metaphase plate.
Anaphase-
-Cohesion proteins are cleaved and the sister
chromatids separate. The chromatids become
chromosomes in their own right.
-The chromosomes begin to move to opposite
poles. The chromosomes are “walking” up the
kinetochore microtubules.
-The kinetochore microtubules are disassembled at
the chromosome end.
-The nonkinetochore microtubules move further
apart as the interact with one another. More
subunits are attached to the overlapping end. This
causes the cell to enlarge.
This experiment shows that the
microtubules are disassembled at the
chromosome end and not the
centrosome end. The spindle fiber were
marked in the middle. If the
microtubules shorten between the mark
and centrosome, then the microtubules
are being reeled in but if the
microtubules shorten between the mark
and the chromosomes, then
microtubules are being disassembled at
that end. The latter is the case. The
kinetochore disassembles the
microtubules at the chromosome end, as
the chromosome “walks” up the
microtubule.
Telophase
-Two daughter nuclei form in the cell.
-Nuclear envelope forms from the
fragments of the disassembled nuclei
and the endomembrane system.
-Chromosomes unwind forming
chromatin.
-Beginning of cytokinesis
Cytokinesis
Mitosis without cytokinesis
results in coencytic bodies
without individual cells.
Happens in some plants, fungi,
algae and even a few animals.
Animals cells do cytokinesis by
the pinching in of the cell
membrane.

In animal cells, rings of actin form under the

cell membrane associated with myosin (much
like skeletal muscles) contracts like a “pull-
string” purse. This forms a cleavage furrow.
Cell Plate in plant cells forms by
fusing vesicles produced by the golgi
Fig. 12-9

Vesicles Wall of 1 m
100 m forming parent cell
Cleavage furrow cell plate Cell plate New cell wall

Contractile ring of Daughter cells

microfilaments Daughter cells
(a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM)