1. Jill before teaching go to this hyperlink (on these words)
THE CELL CYCLE
Picture is of Dolly, a clone.
Procedure involved transferring the nucleus of a specialized cell (in this case a mammary gland cell) into an egg cell whose nucleus had been removed.
Chapter 9

2. Continuous balance between cell division and cell death
Mitosis – A process that forms two genetically identical cells from one
Product of mitosis: daughter cells
Apoptosis – natural cell death – precise – geneticallly programmed(?)

3. The Cell Cycle (hyperlink)
Checkpoints – 1. when certain proteins interact in a way that ensures the proper sequence of events is unfolding
2. allows a pause so newly formed DNA can be checked and repaired before dictating orders
Karyokinesis & cytokinesis can overlap in time, depending upon the species.

4. Cell cycle, con’t Events that occur in the life of a cell.
Includes 3 major stages:
Interphase
Karyokinesis (mitosis)
Cytokinesis

5. Interphase Cell is not dividing, but there is GREAT activity
G1 Phase - carries out basic functions & performs specialized activities.
duration is extremely variable
Synthesizes proteins, lipids and carb in case of cell division
“G” stands for “gap” or “growth”

6. G1 Phase, con’t contains restriction checkpoint ~ cell “decides” to:
Divide
Stops to repair DNA damage
- enter a quiescent phase (G0)
- die

7. Interphase, con’t
G0 Phase – a cell can exit the cycle at G1 to enter this phase
The cell maintains specialized characteristics, but does not divide.
No replication of DNA
Must be at this stage in an egg for cloning to work
Ex. neurons & muscle cells
“S” stands for “synthesis”
Replicated chromosome consists of 2 sister chromatids (exact copies of chromosomal material). Sister chromatids are joined together at a small section of the DNA sequence called the centromere.

8. Interphase, con’t S Phase – Great Synthetic activity – replicating DNA
cell replicates chromosomes & synthesizes associated proteins. (also those that coordinate events of nucleus and cytoplasm
(animal cells replicate centrioles as well)

9. Makes more proteins – especially tubulin for microtubules
G2 Phase –
Makes more proteins – especially tubulin for microtubules
Membrane materials stored in vesicles under the cell membrane
DNA winds tightly around proteins to start mitosis
Interphase ends
Large amounts of tubulin will be required to form microtubules of mitotic spindle.
Illustration = animal cell in G2 interphase.
Photo = plant cell in G2 interphase.

11. Karyokinesis ( aka mitosis hyperlink); M phase)
Equal distribution of replicated genetic material (chromosomes).
Nucleus actively dividing (hyperlink)
See mitotic spindle (diagram pg 141)
Mitosis is a continuous process; is considered in stages for ease of understanding.

12. Participants in Mitosis
Centromere – link sister chromatids

13. Participants, cont
2 identical copies of chromosomes (sister chromatids)

14. Participants, cont Spindle grows from the centrosome/centrioles
Proteins around the centriole initiate spindle growth

15. Mitosis Phases - hyperlink
Prophase (hyperlink)
DNA coils tightly around proteins
replicated chromosomes condense
centrosomes separate & migrate toward opposite sides of cell
mitotic spindle forms (microtubules grow out from centrosomes)
nucleolus disappears
Illustration = animal cell in Prophase.
Photo = plant cell in Prophase.
*Remember, chromosomes were replicated during S phase of interphase.
Centrosome = cloud of proteins (& centrioles in animal cells) that organizes the mitotic spindle.

16. Prometaphase
nuclear membrane breaks down- into small pieces and lay parallel to the cell membrane
spindle fibers attach to centromeres of chromosomes
Once attached, the chromosomes begin moving along the spindle fibers toward the equator of the mitotic spindle.
Illustration = animal cell in Prometaphase.
Photo = plant cell in Prometaphase.

18. chromosomes are lined up single-file along equator of mitotic spindle.
Metaphase
chromosomes are lined up single-file along equator of mitotic spindle.
Chromosomes seem motionless because they are pulled equally by both sides of the cell
Illustration = animal cell in Metaphase.
Photo = plant cell in Metaphase.

19. Anaphase
Centromeres, one per chromatid, move apart separating the chromatids to opposite
Microtubules in the spindle shorten and some lengthen in a way that moves the poles farther apart
Illustration = animal cell in Anaphase.
Photo = plant cell in Anaphase.

20. Telophase mitotic spindle breaks down chromosomes decondense
Cell begins to look like a dumbell (cytokinesis has begun)
mitotic spindle breaks down
chromosomes decondense
nuclear membranes reform around two nuclei
nucleoli reappear
End of Mitosis
Illustration = animal cell in Telophase.
Photo = plant cell in Telophase.

21. 3. Cytokinesis
Distribution of cytoplasm and all other contents to daughter cells.
begins during anaphase or telophase depending on the cell type
differs in animal & plant cells
Cytokinesis overlaps with karyokinesis. It begins during anaphase or telophase depending upon species or cell type.

22. Cytokinesis in animal cells:
cleavage furrow (hyperlink)(slight indentation) forms around equator of cell.
Contractile ring of actin & myosin microfilaments act like a drawstring to pinch the cell in two.
Asters determine the number of cleavage furrows
usually an equal division.

23. Cytokinesis in animal cells

24. Cytokinesis in plant cells hyperlink:
New cell wall must be built
phragmoplast (microtubule structure) forms in cytoplasm & traps vesicles containing cell wall material. (between daughter cells)
vesicles fuse, forming a cell plate across midline of cell.
cell plate gives rise to two primary cell walls.

26. Does cytokinesis always accompany karyokinesis?
Karyokinesis in the absence of cytokinesis results in a syncytium (mass of multinucleated cells).
Usually, but not always.
Examples:
human skeletal muscle tissue (pictured)
endosperm tissue in some plants (nourishes the developing embryo in a seed).

27. Control of the Cell Cycle hyperlink( what turns mitosis on or off)
Checkpoints - groups of interacting proteins that ensure cell cycle events occur in the correct sequence.
Survivins override signals that tell the cell to die, keeping it in mitosis, not apoptosis
Various mechanisms interact to regulate the cell cycle.
Are numerous checkpoints - 4 are described in figure.
Restriction checkpoint - cell “decides” whether to divide, enter G0 phase, or die. Most important checkpoint.
DNA damage checkpoint - turns on genes that manufacture proteins that repair damaged DNA.
Apoptosis checkpoint - necessary to override a signal for the cell to die.
Spindle assembly checkpoint - necessary for construction of spindle & binding of chromosomes to it.

28. Telomeres At tip of chromosomes
100’s-1000’s of repeating sequences on end of chromosome
Each time mitosis occurs, DNA looses sequences
After 50+ divisions DNA signals cell division to cease

30. Telomere, con’t
A few cells, DNA does NOT shrink (bone marrow, small intestine, blood cells, germ cells for sperm)
If DNA shrinks, no telomerase made
Telomerase add DNA to tips of chromosome
Plant cells produce telomerase and divide more than 50 times

31. Shortening of telomeres - loss of telomere DNA signals cell to stop dividing.
Some cells produce telomerase (enzyme that continually adds telomere DNA).
Telomeres are repeating nucleotide sequences found at the tips of chromosomes. Every time a cell divides, some of its telomere DNA is lost. After about 50 divisions (Hayflick limit), a key amount of lost telomere DNA signals cell division to cease.
NOTE: Cells that produce telomerase are able to divide beyond the 50-division limit. They include:
plant cells
cells lining small intestine
bone marrow cells
certain immune system cells
sperm-forming cells
cancer cells

32. Signals to Divide: Signals from outside the cell effect cell cycles
Contact Inhibition - healthy cells stop dividing when they come in contact with other cells.

33. Hormones - stimulate cell division.
Signals to Divide, con’t
Hormones - stimulate cell division.
Ex. Estrogen stimulates uterine cell division
Growth factors - proteins that stimulate local cell division.
Ex. Epidermal growth factor (EGF) stimulates epithelial cell division filling in new skin underneath a scab
Ex. Produced in salivary glands of animals – aids in wound healing
Interaction of kinases & cyclins - activate genes that stimulate cell division.

34. Control at the Tissue level – stem cells and cell populations
Stem Cells (hyperlink)
Cells used to replenish tissues

35. Stem cell’s con’t
When a stem cell divides, one daughter cell will specialize and the other daughter cell will remain a stem cell
Ex: basal layer of skin, bone marrow, & small intestine, heart and ventricles of brain
Cell populations – up to 3% are dividing. (expanding population) or if all are dividing it is called a renewel population
Static populations- cells are no longer dividing in the tissue- nerves and muscles (these enlarge-not divide)

36. B. Apoptosis (hyperlink)
Cell death is part of life
B. Apoptosis (hyperlink)
Programmed cell death; part of normal development.
Eliminates excess cells and cells that could grow uncontrollably.
Tadpole tail, webbing between fingers)
Example of apoptosis:
Feet of embryonic chickens & ducks have webbing between the toes.
Webbing vanishes as the chicken’s foot develops (due to apoptosis).
Webbing is retained as duck’s foot develops.
Apoptosis fine-tunes the human immune system - in the fetus, it destroys T cells that do not recognize self. If they were not destroyed, these T cell would begin attacking the body (autoimmune disease).

37. Steps of Apoptosis: Death receptors activate enzymes called capases.
Capases destroy proteins & various cell components & ready the cell for phagocyte destruction.
From outside, cell rounds up, forms bulges called blebs and fragments (fragments are surrounded by cell membrane, so they don’t initiate an inflammatory response).
Cell death in response to an injury is called necrosis. The cell swells & bursts, initiating an inflammatory response.

38. Apoptosis
rapidly and neatly dismantle cell into membrane bound pieces that phagocyte will mop up
(as opposed to necrosis due to injury
death receoptor receives signal
caspases (enzymes that snip cell components) are activated within
caspases destroy proteins and other components.
caspases destroy adhesion molecules so cell can’t cling to another cell
cell undulates, forming bulges called blebs
nucleus bursts releasing chromatin
cell shatters
loose membrane surrounds pieces
phagocytes mop up
Similar in plant cells, but parts are digested by enzymes

39. Why cells die Brain cell example pg. 158
To distinguish self from non-self
protective function-to detect and weed out cells that could grow uncontrollably

40. C. Cancer (loss of cell cycle control)
Condition resulting from excess cell division or deficient apoptosis.
Characteristics of Cancer Cells:
can divide uncontrollably & eternally
dedifferentiation
are invasive
are heritable & transplantable
lack contact inhibition
readily metastasize
exhibit angiogenesis
exhibit genetic mutability
Cancer cells can divide eternally because they produce telomerase. Cervical cancer cells (HeLa) of Henrietta Lacks who died in 1951 are used extensively in cancer research all over the world today.
Heritability - when a cancer cell becomes cancerous, it passes its loss ov cell cycle control to its descendants.
Transplatability - cancer cells can be injected into a healthy animal; animal will develop cancer because those cancer cells divide to form more cancerous cells.
Cancer cells lack contact inhibition - they tend to form masses called tumors.
Metastasize = ability to spread
Angiogenesis = ability to induce local blood vessel formation.
Cancer cells mutate - a treatment that shrank the original tumor may have no effect on its subsequent growth.

41. Cancer (hyperlink)- con’t
given nutrients and space, cancer cells reproduce uncontrollably
growth rate depends on the type of cell
fast growing must be 1 centimeter in diameter- may produce 1 million new cells/hour
loss of cell cycle control is inherited by descendents
injectable
lack contact adhesion
often undergo mutations
stimulate angiogenesis
(blood vessel growth)

42. mistimed or misplaced mitosis Absence of normal apotosis (hyperlink)
Causes of Cancer:
mistimed or misplaced mitosis
Absence of normal apotosis (hyperlink)
Over-expression of oncogenes
Oncogenes are genes that trigger limited cell division.
Inactivation of tumor suppressor gene
Tumor suppressor genes prevent a cell from dividing or promote apoptosis.
Oncogenes are normally switched off in most cells. They are activated only under certain circumstances (ex. in cells at wound site).
Tumor suppressor genes are normally switched on in most cells. If they are inactivated or removed cells will divide continually or apoptosis does not occur (ex. a childhood kidney cancer is caused by absence of a tumor suppressor gene that normally halts mitosis in kidney tubule cells in the fetus)
Factors that turn on oncogenes or turn off tumor suppressor genes at inappropriate times would lead to development of tumors.

43. Normal functioning of oncogenes & tumor suppressor genes may be affected by environmental factors:
carcinogens
radiation
viruses
diet
exercise habits
Carcinogens = chemicals that cause cancer (tobacco, asbestos, insecticides, saccharine)
Radiation - UV & x-ray photons have enough energy to cause DNA damage.