The process of cell replication
Genes and Proteins
 Proteins
do the work of the cell:
growth, maintenance, response to the
environment, reproduction, etc.
 Proteins are chains of amino acids.
The sequence of amino acids in each
protein is coded in the DNA as a
specific sequence of A, C, G and T
bases: a gene.
 Each gene codes for a different
protein.
Genes and Proteins

Key points:
 All cells within an organism have the
same genes.
 What makes cells different from each
other is that different genes are turned
on and turned off in different cells.

The DNA must be copied and then
divided exactly so that each cell gets an
identical copy.
MITOSIS VS. MEIOSIS
 Mitosis
is normal cell division, which
goes on throughout life in all parts of
the body. Meiosis is the special cell
division that creates the sperm and
eggs, the gametes. We will discuss
meiosis separately.
 Mitosis and meiosis occur in
eukaryotes. Prokaryotes use a
different method—”binary fission” to
divide.
NUMBERS OF CHROMOSOMES

Humans have 46 chromosomes
 23 from each parent
 Every cell has the same 46
chromosomes
 Each species has a characteristic
number of chromosomes:
○ corn has 20,
○ house flies have 10,
○ chimpanzees have 48.
SOME VOCABULARY
 Chromosomes
exist in 2 different
states:
 Chromatin: Between cell divisions,
DNA/protein complex is loosely
coiled (easier for protein synthesis)
 Chromatid: Right after DNA
replication, the chromosomes are
tightly coiled together (it is easier to
“arrange” chromosomes this way)
 There are 2 copies of the
chromosome
 Centromere: The two copies of the
chromatid after replication are held
together by the centromere.
CELL CYCLE
Some cells divide constantly: cells in the
embryo, skin cells, gut lining cells, etc.
Other cells divide rarely or never: only to
replace themselves.
 Actively dividing cells go through a cycle
of events that results in mitosis. Most of
the cycle was called “interphase” by the
microscopists who first studied cell
division. During interphase the cell
increases in size, but the chromosomes
are invisible.
 The 3 stages of interphase are called
G1, S, and G2.

INTERPHASE
 Interphase
is the normal part
of cellular function. It includes
the following (about 90% of
cell life):
 G1 phase
 S phase
 G2 phase
http://www.biology.arizona.edu/cell_bio/tutorials/cell_cycle/cells2.html
MITOSIS
G2
(Gap 2)
1
M
2
G1
(Gap 1)
G0
S-Phase
(DNA SelfReplication)
THE
CELL
CYCLE
G1 (GAP 1) PHASE
(“Gap”) is the period between
mitosis and S, when each
chromosome has 1 chromatin (not
chromatid). Cells spend most of their
time in G1: it is the time when the cell
grows and performs its normal
function. Control of cell division
occurs in G1: a cell that isn’t destined
to divide stays in G1, while a cell that
is to divide enters the S phase.
 G1
S PHASE
S phase (“Synthesis”) is the time
when the DNA is replicated, when the
chromosome goes from having one
chromatin to having 2 chromatids held
together at the centromere.
 The
G2 (GAP 2) PHASE
 G2
is the period between S and
mitosis. The chromosome have 2
chromatids, and the cell is getting
ready to divide.
HOW TO IDENTIFY
INTERPHASE
nucleolus (if any)
still visible
Interphase
nuclear envelope
clearly visible
chromatin,
NO
chromosomes,
yet
http://www.fed.cuhk.edu.hk/~johnson/photomicrographs/mitosis/animal/animal_interphase.htm
INTERPHASE
http://iccbweb.med.harvard.edu/mitchisonlab/Pages/mt.html
interphase
interphase
INTERPHASE
Allium root tip
Coregonus blastula
INTERPHASE is the
normal lifetime of a
cell, after being
“born” by division,
and before it divides
itself.
INTERPHASE is not
a stage of mitosis !
Biological Science, a Molecular Approach.
BSCS Blue Version. Heath and Company, 1996.
What is MITOSIS ?
THE PROCESS BY WHICH TWO NEW
NUCLEII ARE FORMED, WITH EXACTLY
THE SAME KIND AND NUMBER OF
CHROMOSOMES AS THE PARENT CELL.
(1 CELL TO 2 CELLS)
http://fairmanstudios.com/als.htm
STEPS IN MITOSIS (In AP, the
phases are not emphasized)
PROPHASE
METAPHASE
ANAPHASE
TELOPHASE
PROPHASE

In prophase, the cell begins the process of
division.
 The chromosomes condense. The
proteins attached to the DNA cause the
chromosomes to go from long thin
structures to short fat one, which makes
them easier to pull apart (VISIBLE).
 The nuclear envelope disappears. The
double membrane that surround the
nucleus dissolves into a collection of
small vesicles, freeing the chromosomes
to use the whole cell for division
 Centrosomes form and move to opposite
poles. During interphase, the pair of
centrosomes were together just outside
the nucleus. In prophase they separate
and move to opposite ends of the cell.
 The spindle starts to form, growing out of
the centrosomes towards the
chromosomes.
PROMETAPHASE
 Nuclear
membrane fragments
 Spindle interaction with chromosomes
 Kinetochore develops at the
centromere (this is where the spindle
microtubules are going to bind)
HOW TO IDENTIFY
PROPHASE
PROPHASE
•Nuclear membrane dissolves.
•Nucleolus disappears.
•Chromosomes form.
•Centrioles migrate & form spindle.
http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/mitosis_F.01/mitosis.html
PROPHASE
nuclear envelope
disappears
nucleolus
disappears
http://www.ac-dijon.fr/pedago/svt/documents/mitose/prophase.gif
chromosomes
become visible
PROPHASE
http://www.itg.uiuc.edu/technology/atlas/structures/mitosis/prophase.htm
PROPHASE
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METAPHASE

Metaphase is a short
resting period where
the chromosomes are
lined up on the
equator of the cell,
with the centrosomes
at opposite ends and
the spindle fibers
attached to the
kinetochore.
Everything is aligned
for the rest of the
division process to
occur.
HOW TO IDENTIFY
METAPHASE
METAPHASE
chromatids
spindle
centriole
http://www.chembio.uoguelph.ca/educmat/chm736/cycletx.htm
•chromatids line up on the equator.
METAPHASE
TWO IDENTICAL COPIES OF ONE CHROMOSOME.
THIS
CHROMATID
WILL SOON
MOVE TO
NORTH POLE
THIS
CHROMATID
WILL SOON
MOVE TO
SOUTH POLE
http://genenlab.spoono.com/gnu/mandm.shtml
chromatids
spindle
centriole
Nature (408. 423, 2000).
http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/mitosis_F.01/mitosis.html
METAPHASE
http://iccbweb.med.harvard.edu/mitchisonlab/Pages/mt.html
METAPHASE
Allium root tip
Coregonus blastula
ANAPHASE

In anaphase, the
centromeres divide.
At this point, each
individual
chromosome goes
from:
 1 chromosome with 2
chromatids to:
 2 chromosomes with
one chromatid each.

Then the spindle
fibers contract, and
the chromosomes are
pulled to opposite
poles, towards the
centrosomes.
HOW TO IDENTIFY
ANAPHASE
ANAPHASE
•chromatids migrate
to each pole.
http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/mitosis_F.01/mitosis.html
ANAPHASE
http://www.univ-orleans.fr/SCIENCES/BIOCHIMIE/MMC/accueil.htm
ANAPHASE
early
Conly Rieder http://www.wadsworth.org/BMS/SCBlinks/WEB_MIT2/HOME.HTM
late
ANAPHASE
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TELOPHASE





In telophase the cell actually
divides.
The chromosomes are at the
poles of the spindle.
The spindle disintegrates
The nuclear envelope re-forms
around the two sets of
chromosomes (become less
coiled).
The cytoplasm is divided into 2
separate cells, the process of
cytokinesis.
CYTOKINESIS




The organelles (other than the
chromosomes) get divided up into the 2
daughter cells passively: they go with
whichever cell they find themselves in.
Plant and animal cells divide the
cytoplasm in different ways.
In plant cells, a new cell wall (CELL
PLATE)made of cellulose forms
between the 2 new nuclei, about where
the chromosomes lined up in
metaphase. Cell membranes form
along the surfaces of this wall. When
the new wall joins with the existing side
wall, the 2 cells have become separate.
In animal cells, a ring of actin fibers
(microfilaments are composed of actin)
forms around the cell equator and
contacts, pinching the cell in half.
(CLEAVAGE FURROW)
CELL CYCLE CONTROL

These will control whether a cell divides
or not
 Growth Factor: a protein that is released
that induces a cell to divide (cell
communication)
 Density-Dependent Inhibition: if an area is
too crowded with cells, cell division is
inhibited. If the area lacks cells, division is
allowed to occur
 Anchorage Dependence: must be attached
to a substrate
HOW TO IDENTIFY
TELOPHASE
TELOPHASE
•Chromosomes dissolve.
•Mitotic spindle dissolves.
•Nuclear membrane forms.
•New nucleoli form.
TELOPHASE
ONE
DAUGHTER
NUCLEUS
FORMS AT
NORTH POLE
SPINDLE
APPARATUS
DISSOLVES
ONE
DAUGHTER
NUCLEUS
FORMS AT
SOUTH POLE
TELOPHASE
early
late
New nuclei form at
the poles.
Cytokinesis
begins.
http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/mitosis_F.01/mitosis.html
TELOPHASE
TELOPHASE
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Summary of Mitosis

Prophase:
○
○
○
○

Metaphase
○
○

Chromosomes condense
Nuclear envelope disappears
centrosomes move to opposite sides of the cell
Spindle forms and attaches to centromeres on the chromosomes
Chromosomes lined up on equator of spindle
centrosomes at opposite ends of cell
Anaphase
○
Centromeres divide: each 2-chromatid chromosome becomes two 1-chromatid
chromosomes
○ Chromosomes pulled to opposite poles by the spindle

Telophase
○
○
○
Chromosomes de-condense
Nuclear envelope reappears
Cytokinesis: the cytoplasm is divided into 2 cells
http://www.dartmouth.edu/artsci/bio/cbbc/courses/bio4/bio4-lectures/theCell.html
1
2
CYTOKINESIS
MITOSIS is
about
organizing and
distributing
CHROMOSOMES
Cancer


Cancer is a disease of uncontrolled cell division. It starts
with a single cell that loses its control mechanisms due to a
genetic mutation. That cell starts dividing without limit, and
eventually kills the host.
Normal cells are controlled by several factors.
 Normal cells stay in the G1 stage of the cell cycle until
they are given a specific signal to enter the S phase, in
which the DNA replicates and the cell prepares for
division. Cancer cells enter the S phase without waiting
for a signal.
 Normal cells are mortal. This means that they can divide
about 50 times and then they lose the ability to divide, and
eventually die. This “clock” gets re-set during the
formation of the daughter cells. Cancer cells escape this
process of mortality: they are immortal and can divide
endlessly.
 Normal cells that suffer significant chromosome damage
destroy themselves due to the action of a gene called
“p53”. Cancer cells either lose the p53 gene or ignore its
message and fail to kill themselves.
Cancer Progression
There are many different forms of cancer, affecting different
cell types and working in different ways. All start out with
mutations in specific genes called “oncogenes”. The normal,
unmutated versions of the oncogenes provide the control
mechanisms for the cell. The mutations are caused by
radiation, certain chemicals (carcinogens), and various
random events during DNA replication.
 Once a single cell starts growing uncontrollably, it forms a
tumor, a small mass of cells. No further progress can occur
unless the cancerous mass gets its own blood supply.
“Angiogenesis” is the process of developing a system of small
arteries and veins to supply the tumor. Most tumors don’t
reach this stage.
 A tumor with a blood supply will grow into a large mass.
Eventually some of the cancer cells will break loose and move
through the blood supply to other parts of the body, where they
start to multiply. This process is called metastasis. It occurs
because the tumor cells lose the proteins on their surface that
hold them to other cells.

How is cancer harmful?


What are the ways in which cancer is harmful?
Some examples:
 Lung cancer can damage the surrounding tissue
and prevent the normal functioning of the lung
until it collapses or fails
 Stomach cancer can prevent the uptake of
nutrients and cause loss of food uptake
 Bone cancer can prevent the creation of blood
cells
 Some cancers create “chemcials” that can
disrupt the delicate balance of the body
 Some cancers can lead to infections
Cancer Treatment
Two basic treatments: surgery to remove the tumor,
and radiation or chemicals to kill actively dividing cells.
 It is hard to remove all the tumor cells. Tumors often
lack sharp boundaries for easy removal, and metastatic
tumors can be very small and anywhere in the body.
 Radiation and chemotherapy are aimed at killing
actively dividing cells, but killing all dividing cells is
lethal: you must make new blood cells, skin cells, etc.
So treatment must be carefully balanced to avoid killing
the patient.
 Chemotherapy also has the problem of natural
selection within the tumor. If any of the tumor cells are
resistant to the chemical, they will survive and multiply.
The cancer seems to have disappeared, but it comes
back a few years later in a form that is resistant to
chemotherapy. Using multiple drugs can decrease the
risk of relapse: it’s hard for a cell to develop resistance
to several drugs at the same time.

WHAT DO YOU THINK?
 What
do you think would be the
OVERLYING purpose of cancer
research?
 What do you think are the major
strategies to “cure” cancer?
DEXOSOMES
Create dendritic cells
2. Induce the production of dexosomes
(activates immune system)
3. Load the dexosomes with a peptide
(protein that is found on a marker for
cancer cells . . . acts as an antigen)
4. The peptide loaded dexosomes activate
your immune system to attack and
destroy cancer cells.
1.