M I T O S I S

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t h e M - p h a s e
M I T O S I S
The process of cell replication
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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.

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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.

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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 methodbinary
  fission to divide.

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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.

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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.

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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.

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INTERPHASE

• Interphase is the normal part of cellular
  function. It includes the following (about 90
  of cell life)
• G1 phase
• S phase
• G2 phase

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http//www.biology.arizona.edu/cell_bio/tutorials/
cell_cycle/cells2.html
metaphase
anaphase
telophase
prophase
M I T O S I S
1
G2 (Gap 2)
M
cytokinesis
2
G1 (Gap 1)
THE CELL CYCLE
G0
S-Phase (DNA Self- Replication)
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G1 (GAP 1) PHASE

• G1 (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 isnt destined
  to divide stays in G1, while a cell that is to
  divide enters the S phase.

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S PHASE

• The 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.

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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.

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Pictures of cells during interphase

• HOW TO IDENTIFY INTERPHASE

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nucleolus (if any) still visible
Interphase
nuclear envelope clearly visible
chromatin, NO chromosomes, yet
http//www.fed.cuhk.edu.hk/johnson/photomicrograp
hs/mitosis/animal/animal_interphase.htm
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INTERPHASE
http//iccbweb.med.harvard.edu/mitchisonlab/Pages/
mt.html
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interphase
interphase
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INTERPHASE
Allium root tip
Coregonus blastula
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INTERPHASE is the normal lifetime of a cell,
after being born by division, and before it
divides itself.
MITOSIS
INTERPHASE is not a stage of mitosis !
Biological Science, a Molecular Approach. BSCS
Blue Version. Heath and Company, 1996.
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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
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STEPS IN MITOSIS (In AP, the phases are not
emphasized)

• PROPHASE
• METAPHASE
• ANAPHASE
• TELOPHASE

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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.

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PROMETAPHASE

• Nuclear membrane fragments
• Spindle interaction with chromosomes
• Kinetochore develops at the centromere (this is
  where the spindle microtubules are going to bind)

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Pictures of cells during prophase

• HOW TO IDENTIFY PROPHASE

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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
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PROPHASE
nuclear envelope disappears
nucleolus disappears
chromosomes become visible
http//www.ac-dijon.fr/pedago/svt/documents/mitose
/prophase.gif
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PROPHASE
http//www.itg.uiuc.edu/technology/atlas/structure
s/mitosis/prophase.htm
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PROPHASE
Coregonus blastula
Allium root tip
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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.

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Pictures of cells during metaphase

• HOW TO IDENTIFY METAPHASE

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METAPHASE
chromatids
spindle
centriole
http//www.chembio.uoguelph.ca/educmat/chm736/cycl
etx.htm

• chromatids line up on the equator.

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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
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chromatids
spindle
centriole
Nature (408. 423, 2000).
http//www.blc.arizona.edu/courses/181gh/Lectures_
WJG.01/mitosis_F.01/mitosis.html
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METAPHASE
http//iccbweb.med.harvard.edu/mitchisonlab/Pages/
mt.html
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METAPHASE
Coregonus blastula
Allium root tip
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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.

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Pictures of cells during ANAPHASE

• HOW TO IDENTIFY ANAPHASE

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ANAPHASE

• chromatids migrate
• to each pole.

http//www.blc.arizona.edu/courses/181gh/Lectures_
WJG.01/mitosis_F.01/mitosis.html
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ANAPHASE
http//www.univ-orleans.fr/SCIENCES/BIOCHIMIE/MMC/
accueil.htm
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ANAPHASE
early
late
Conly Rieder http//www.wadsworth.org/BMS/SCBlink
s/WEB_MIT2/HOME.HTM
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ANAPHASE
Coregonus blastula
Allium root tip
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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.

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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)

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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

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Pictures of cells during ANAPHASE

• HOW TO IDENTIFY TELOPHASE

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TELOPHASE
http//www.bmb.psu.edu/courses/bisci2/mitosis/mito
sis.htm

• Chromosomes dissolve.

• Mitotic spindle dissolves.

• Nuclear membrane forms.

• New nucleoli form.

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TELOPHASE
ONE DAUGHTER NUCLEUS FORMS AT NORTH POLE
ONE DAUGHTER NUCLEUS FORMS AT SOUTH POLE
SPINDLE APPARATUS DISSOLVES
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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
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TELOPHASE
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TELOPHASE
Coregonus blastula
Allium root tip
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Summary of Mitosis

• Prophase
• Chromosomes condense
• Nuclear envelope disappears
• centrosomes move to opposite sides of the cell
• Spindle forms and attaches to centromeres on the
  chromosomes
• Metaphase
• 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

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http//www.dartmouth.edu/artsci/bio/cbbc/courses/b
io4/bio4-lectures/theCell.html
1
2
CYTOKINESIS
MITOSIS is about organizing and distributing
CHROMOSOMES
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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.

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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 dont 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.

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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

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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 its hard for a cell to develop
  resistance to several drugs at the same time.

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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?

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DEXOSOMES

1. 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.