Cell Cycle
Why Cells Divide
 Why
do cells need to divide?
Cell Division - Purpose
 Provides
a means of
reproduction for organisms.
 Provides a means of growth in
multicellular organisms.
 Provides a means of repair in
multicellular organisms.
Reproduction
 Unicellular
organisms divide in
order to form new organisms.
No
Elizabeth,
don’t go!
Apologies to Gary Larson and the FAR SIDE
Reproduction

Multicellular organisms divide to
reproduce special cells (gametes)
that will carry out the formation of
a new organism.
Growth
 Multicellular
organisms are
made of millions to trillions of
microscopic cells rather than a
few large cells. Growth mainly
occurs by increasing the
number of cells.
Repair
 Many
microscopic cells as
opposed to only a few large
ones is also advantageous in
the case of injury.
How so?
Is there any advantage to
possessing many small cells as
opposed to a few large cells?
Examine the two cells below. The blue color
represents the area of diffusion of glucose within
the cell over equal periods of time. Do you see a
potential problem that might suggest an answer
to the question above?
nucleus
Surface Area to Volume Ratio
Relative size of the surface area of
the plasma membrane and the
volume of the cell reach a critical
point.
L
W
H
Analyze the
Day 1
1
1
following cubic cell: one
1.
Day 2
two
2
2
Nuclear Limitations
2.
Limited capability of the
nucleus
-- there is a finite amount of
genetic material because the
genome size remains
constant even as the cell
grows.
Why Cells Divide
 What
actually triggers or cues
the cell about the need to
divide?
Most of it comes down to chemicals.
Why Cells Divide

Two irreversible points in cell cycle
– replication of genetic material
– separation of sister chromatids

REPLICATION (S phase)

SEPARATION (anaphase)
Why Cells Divide

Checkpoints
– process is assessed & possibly halted

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?

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
Why Cells Divide
The “decision” to divide has
both external and internal
chemical influences.
Why Cells Divide
 EXTERNAL
–Cells can have direct contact
with each other through cell
junctions or surfaces.
–Certain chemicals can easily
come in contact with adjacent
cells in this way.
Why Cells Divide
 Cells
can communicate with
each other by secreting
chemical messengers into the
extracellular fluid.

Paracrine signaling
–
Hormonal signaling
–
(ex. Adjacent cells)


target is near the signaling source
signal travels through bloodstream
from source to target (pituitary – ovaries)
Synaptic signaling – chemicals travel across small “gap” or
synapse (neurotransmitters from neuron to neuron)
Why Cells Divide


1.
The signaling process consists
of 3 stages:
EXTERNAL
Reception - Chemical messengers
interact with receptors, often those
of the plasma membrane.
Why Cells Divide
INTERNAL
2. Transduction- This begins a chain
of events in a chemical pathway
within the cell, such as a
“phosphorylation cascade”
– Phosphorylation cascading refers to the
transfer of phosphate groups from one protein
molecule to the next, via a type of kinase
enzyme, subsequently activating the molecules
in the pathway. (Think Domino effect)
Why Cells Divide
3.
Response - cellular activity
– Could be:
 Rearrangement of cytoskeleton
 Opening/closing ion channels
 Initiation of metabolic activity,
such as cell division.
Chemical Regulation of
the Cell Cycle

Once signaled, Kinase* proteins
give the go ahead signals at G1
and G2 checkpoints.
– *Kinase proteins are a family of
related proteins that activate
proteins which in turn activate
certain cell processes such as cell
division.
 These
kinases (Cdks)
themselves are not activated
until they are attached to
cyclin (becoming MPFs)
 Cyclin concentrations fluctuate
within a cell, slowly building up
until cell division begins.
 The
MPF’s (Cdk-cyclin) cause
nuclear membrane destruction
and stimulate other kinases,
setting the chain of events in
motion known as mitosis.
The Cell Cycle (Internet click here)
(click on the words above to go to website and ACQUIRE
more information on the cell cycle.)
 Consists
of phases
characterized by important
events in the life of a cell
After Mitosis




MPFs (partially made of cyclin) levels must
drop to allow the cell to enter interphase
again.
Proteins such as ubiquitin*, regulate the
cycle by causing the degradation of cyclin
and kinases.
This brings about the end of mitosis and the
reforming of the nuclear membrane.
Thus the new cells continue to interphase.
*Ubiquitin – common across most eukaryotic species; hence
ubiquitous.
Other Division Halting Processes
Density-dependent inhibition –
when the cell density reaches
a certain maximum, many
cells stop dividing.
Anchorage dependence –
contact with a substratum
may influence if a cell stops
dividing.
External signals

Growth factors
– coordination between cells
– protein signals released by body
cells that stimulate other cells to
divide

density-dependent inhibition
– crowded cells stop dividing
– each cell binds a bit of growth factor
 not enough activator left to trigger
division in any one cell
 Degradation of protein growth
factors also possible

anchorage dependence
– to divide cells must be attached to a
substrate
 “touch sensor” receptors
Example of a Growth
Factor

Platelet Derived Growth Factor (PDGF)
– made by platelets in blood clots
– binding of PDGF to cell receptors stimulates cell
division in connective tissue

heal wounds
Other Division Halting Processes
Necrosis and Apoptosis
 Necrosis – death due to insult/injury
 Apoptosis – programmed cell death
 What benefits would there be for an
organism to destroy its own cells?


http://virtuallaboratory.colorado.edu/Biofundament
als/lectureNotes/Topic5-4_CellDeath.htm
Cancer



Transformation – Alterations in genes
implicated with cell cycle begin the
conversion of a normal cell to
cancerous cell.
Oncogenes
Tumor Supressor genes
– Tumor – mass of abnormal cells
Benign – tumor remains at site
 Malignant – Becomes invasive enough to
interfere with organ function
 Metastasis – cancer cells spread to other sites

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
– immortality = unlimited divisions

turn on chromosome maintenance genes
– promotes blood vessel growth

turn on blood vessel growth genes
– overcome anchor & density dependence

turn off touch-sensor gene
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
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.
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.


Explain the purpose of meioisis.
Compare and contrast the processes of
mitosis and meiosis.
 Distinguish between male and female
gametogenesis in humans.
 Define tetrad, homologous chromosome,
synapsis.
 Describe the process of crossing-over.
 Identify the composition of a eukaryotic
chromosome.
 Explain the results of a duplication,
deletion, inversion and translocation of
chromosomes.
 Define nondisjunction and provide
examples of several genetic disorders
resulting from nondisjunction.
Genomes and
Chromosomes
A Closer Look at Reproduction
Genomes and Chromosomes
 An
organism is determined by
its organism’s genetic material
or genome.
 In order to maintain life, any
new cells created must
possess the same exact
genome.
Genome and Chromosomes
 The
mitotic portion of the cell
cycle ensures that the genome
is transferred correctly to the
new cells created.
http://images.sciencedaily.com/2009/10/091005
110401-large.jpg
Genes and Chromosomes
Chromosomes are the
condensed version of the
DNA-protein complex called
chromatin.
http://www.damours.iric.ca/Site/Projects_files/Chromatin_Nucleosomes.png
Genes and Chromosomes

Once the
chromatin is
replicated during
the S phase of
the cell cycle a
cell is ready to
divide.
Kinetochore
Mitosis vs. Meiosis
Mitosis
Meiosis
Both
Mitosis vs. Meiosis
Mitosis
Chromosome
Replication
Cell
division –
end cell #
Chromosome
Result
Both
Meiosis
During S
phase
Once -two
Same as
original:
Diploid
Twice –four
Half of the
originalhaploid
Meiosis
For what purposes would
“HALF” the chromosome
material be appropriate?
For the union of two cells
(gametes) – sexual reproduction.
Meiosis I
 Homologous
Chromosomes
pair up forming a “tetrad” in a
process called synapsis.
 At certain points the
chromatids of the homologs
may crisscross, forming a
chiasmata.
Meiosis I
 As
the cell transists from
metaphase to anaphase it is
the homologs which are
separated rather than the
chromatids.
Meiosis I
 Cytokinesis
occurs, resulting in
two haploid cells.
 Depending on the type of
gamete, meiosis II may
proceed directly or be carried
out at a later date.
Meiosis II
 Proceeds
much like the
process of mitosis, however,
the end results differ due to
Meiosis I.
4 haploid cells are created.
Meiosis
 Humans
–
–Spermatogenesis – 4 viable
haploid sperm produced.
–Oogenesis – 1 viable haploid
egg and 3 non-functional
polar bodies produced.
What is the advantage of producing one LARGE egg as opposed to 4 smaller ones?
http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/gametogenesis.jpg
Meiosis
 Plants
– produce spores which
then mitotically divide to form
gametophyte. This produces
gametes which then fuse to
form sporophyte.
Genetic Variation
 Does
not exist in cells
produced by mitosis, unless
some mutation arises.
 Sexual reproduction provides a
recombination of genetic
material in 3 ways.
Genetic Variation

Independent assortment of
homologues.
Genetic Variation

Random joining of gametes.
Getting
here is only
HALF the
race
Boys!
Genetic Variation

Crossing over,
as demonstrated in lab activity,
involves the exchange of genetic
material between nonsister
chromatids, during prophase I
Genetic Variation
 Deletion
and duplication –
see lab activity
 Inversion–
see lab activity
CHROMOSOMES,
KARYOTYPES, AND
SEXUAL LIFE
CYCLES
KARYOTYPE
“CARTOONIZED”
Ideogram of
chromosome
after staining.
The short arm of
the chromosome
is referred to as
“p” and the long
arm as “q”.
KARYOTYPE


ORDERED DISPLAY OF AN
INDIVIDUAL’S CHROMOSOMES.
PREPARED BY TREATING CELLS WITH
DRUG TO STIMULATE MITOSIS AND
THEN ADDING ANOTHER TO STOP IT
AT METAPHASE.
KARYOTYPE
 CAN
BE USED TO DIAGNOSE
CERTAIN GENETIC
DISORDERS (SUCH AS
ANEUPLOIDY CAUSED BY
NONDISJUNCTION).
KARYOTYPES
COLOR ENHANCED BY COMPUTER
KARYOTYPES
CHROMOSOME LENGTH,
SHAPE, AND POSITION OF
CENTROMERE USED FOR
IDENTIFICATION.
•BANDING
CREATED BY
THE USE OF
DYES.
•USED TO
IDENTIFY
SPECIFIC
CHROMOSOMES.
KARYOTYPES
What can
you
determine
about this
individual?
KARYOTYPES
What can
you
determine
about this
individual
?
KARYOTYPES
What
about this
individual
?
KARYOTYPES
LASTLY,
WHAT
ABOUT THIS
INDIVIDUAL
?
Sexual Life Cycles




Many organisms, other than animals,
sexually reproduce.
Sexual reproduction is a way to
increase variety within a population.
This can then lead to evolution of the
populations themselves.
The sexual life cycle itself, has been
subject to evolutionary changes.