Key Points - Cell cycle and cancer
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The cell cycle is a continual process that is divided into 2 major stages
1. Interphase
- when cell prepares for division by replicating DNA and other sub-cellular organelles and
making proteins needed for mitosis and cell division
- divided into two Gap or GROWTH phases G1 and G2, and a Synthesis phase called S
- cells can progress from G 1 to S or can exit G1 and enter G0, a quiescent stage
characterized by no replication of DNA
- during G1 and G2 the cell synthesizes proteins and membranes needed for chromosome
and cell division
- during S phase the chromosomes are replicated by DNA polymerase
2. Mitosis - see the University of Arizona Biology Project for review of mitosis
http://www.biology.arizona.edu/cell_bio/tutorials/cell_cycle/cells3.html
Regulation of the cell cycle
The control of cell division is very complex. The passage of a cell through the cell cycle is
controlled by proteins in the cytoplasm, such as cyclins and cyclin-dependent kinases.
• Cyclins - proteins whose levels rise and fall (cycle) during the cell cycle. For
example, there is a cyclin that is present at high level in G1 but then its levels are
low in S and G2, and there is a different cyclin that is high in S phase but its levels
are low in G1 and G2.
• Cyclin-dependent kinases (Cdks) - the levels of these proteins remain stable
throughout the cell cycle, but each must bind the appropriate cyclin in order for its
enzyme activity to be turned on. Cyclin:Cdk protein complexes add phosphate
groups to proteins that function in the cell cycle. Phosphorylation of the substrate
promotes or reduces the activity of the proteins that regulate the cell cycle.
• The anaphase-promoting complex (APC) promotes transition through anaphase.
Steps in the cell cycle
1. The G1 cyclin protein levels increase, the G1 cyclin binds a Cdk and signals the cell to
prepare for DNA replication.
2. Rising level of the S-phase cyclin binds to a Cdk, enters the nucleus and tells the cell to
duplicate its DNA (and its centrosomes).
3. As DNA replication continues, the S-phase cyclin is degraded, and the levels of mitotic
cyclins begin to rise.
4. The protein complex containing the mitotic cyclin and the M-phase Cdk signals the cell
to initiate assembly of the spindle, breakdown the nuclear membrane and condense the
chromosomes.
5. The mitotic cyclin/M-phase Cdk complex also activates the anaphase-promoting
complex allowing the sister chromatids at the metaphase plate to separate and move to
the poles and prepare the cell for the next G 1.
Key Points - Cell cycle and cancer
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G zero G0 - Phase where cells go when they stop dividing, temporarily or permanently. A
G0 cell is often called quiescent or resting. However, many are busy carrying out their
functions in the organism, e.g., secretion, attacking pathogens. Some G0 cells re-enter the
cell cycle. Cancer cells cannot enter G0 and are destined to repeat the cell cycle
indefinitely.
Checkpoints: Quality Control of the Cell Cycle
The cell has several checkpoints for interrupting the cell cycle if something goes wrong.
Mutations in the genes encoding the proteins required for the cell-cycle checkpoints can
cause cancer.
•
DNA damage checkpoint: senses DNA damage before the cell enters S phase and
during S phase. When the cell senses DNA damage, the cell cycle is stopped until
the damage is repaired. If the damage is so severe that it cannot be repaired, the
cell self-destructs by apoptosis (programmed cell death). p53 is a protein that
functions in the DNA-damage checkpoint by blocking the cell cycle if DNA is
damaged. If the DNA damage is severe, p53 can cause apoptosis.
•
DNA replication checkpoint: If replication stops due to a problem, the cell cycle is
halted until the problem is resolved.
•
Spindle checkpoints: Detect problems with spindle fibers attaching to
kinetochores, arrests in metaphase until all kinetochores can be attached correctly,
will trigger apoptosis if the damage is irreparable.
Skin cancer
Cancer is a disease where regulation of the cell cycle goes awry and normal cell growth and
behavior is lost. Skin cancer is the most common cancer in the United States. According
to the National Cancer Institute (NCI), over one million people in the U.S. are diagnosed
with skin cancer every year. The NCI says skin cancer is now almost 100 percent curable
if found early and treated promptly.
UV light
Much of the damage to DNA in skin cells is caused by ultraviolet (UV) radiation found in
sunlight, in tanning lamps and tanning beds. UV light is divided into three wavelength
bands, ultraviolet A (UVA), ultraviolet B (UVB) and ultraviolet C (UVC). Only UVA and UVB
rays reach the earth. UVC radiation is absorbed by atmospheric ozone. UVA and UVB
rays cause the damage that can lead to skin cancer.
UV effects on DNA and Gene Expression
UV light changes the behavior of skin cells by changing the expression of genes and
damaging DNA. UV radiation causes DNA damage, causing the formation of thymine
dimers, pyrimidine dimers, 6-4 photoproducts and single-strand breaks. Protective
Key Points - Cell cycle and cancer
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proteins in cells, such as p53, can stop damaged cells from proliferating and promote the
repair of damaged DNA.
Protective measures against skin cancer
• Avoid sunburns
• Avoid tanning parlors
• Use protective clothing and sunscreens
• Have your doctor check suspicious skin lesions
Sunscreens - 2 main types:
Physical: opaque pastes and creams that reflect or scatter incident UV rays. Ex: zinc
oxide, titanium dioxide and magnesium silicate. Protect against both the UVB and UVA.
Chemical: act by absorbing UVB rays - para-aminobenzoic acid (PABA), PABA esters,
salicylates, cinnamates, anthranilates and the benzophenones.
Other factors may contribute to skin cancer
Sun exposure doesn't explain melanomas or other skin cancers that develop on skin not
exposed to sunlight. Heredity may play a role. Skin cancer can also develop from exposure
to toxic chemicals or as a result of radiation treatments.
Possible exam questions:
1. List two types of proteins that regulate the cell cycle.
2. The type of light from tanning booth lamps or the sun that causes DNA damage that
can lead to skin cancer is called_____________________.
3. Cells that are not actively dividing but are carrying out their normal functions in an
organism are in:
A. G 1 phase
B. G2 phase
C. S phase
D. G0 phase