Controlling the Cell Cycle

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What is the cell control system?

A group of proteins that regulate the cell cycle.

How does the cell internally regulate itself?

By using three checkpoints, G1, G2, M.

What happens if the conditions of the checkpoints are not met?

The cell will not enter the next phase of the cell cycle.

G1 Checkpoint (restriction)

End of G1

* Are there adequate resources (nucleotides) for division? Is the cell large enough? Has the DNA been damaged?

G2 Checkpoint

End of G2

* Are there adequate resources (mitotic proteins) for division? Is the cell large enough? Has the DNA been damaged?

M Checkpoint

End of Metaphase

* Have the spindle fibres attached correctly to the chromatids? Are the chromosomes aligned correctly?

External Cell Cycle Controls

* Molecular signals: contact with other cells, tumours release signalling molecules, hormones promote cell division in tissue.
* Environmental conditions: pH levels, temperature, nutrients.

What happens if uncontrolled cell division occurs in a mature organism?

A neoplasm may form.

What is a neoplasm?

An abnormal growth of tissue that can form a mass, for example a tumour. They can eventually become cancer.

What exactly is cancer?

Unregulated and abnormal cell division. It is commonly caused by the increased rate of cell division or the suppression of apoptosis.

Benign Neoplasm

Form localised masses but do not transform into cancer.

Potentially Malignant Neoplasm

Form localised masses that **will eventually** invade other tissues and transform into cancer.

Malignant Neoplasms

Form masses that invade other tissues and transform into cancer.

How are cancer cells different from normal cells?

* Faster division
* Less specialised
* Develop their own blood supply
* DNA mutations occur
* No limited number of divisions
* Can spread to other parts of the body.

What are proto-oncogenes?

They control the stimulation of cell growth and are required for normal growth and development.

Causes of Cancer: Genetic Factors

* Mutations to proto-oncogenes: mutation turns them to oncogenes that promote uncontrolled cell division
* Mutations to tumour suppressor genes
* Hereditary cancers: when someone inherits mutated genes.

Mutagens

Environmental factors that can damage DNA.

Carcinogens

Cancer causing agents.

Causes of Cancer: Environmental Factors

* Chemical: tobacco, air pollution
* Physical: X-Rays, UV light
* Biological: Viruses

Apoptosis

Programmed cell death, highly coordinated process that does not spill cell contents or trigger an immune response.

Why does Apoptosis occur?

* Cells which are damaged or defective must be eliminated.
* During fetal development, the removal of excess cells.

What are Caspases?

Apoptotic Enzymes

What is Phagocytosis?

The breakdown of apoptotic bodies by the phagocytes.

Major Steps of Apoptosis

1. Activation of caspases and begin breakdown of cell contents.
2. Cell shrinks and blebs begin to form.
3. Cells continue to shrink and package themselves into apoptotic bodies.
4. Phagocytosis.

Necrosis

Accidental and uncontrolled cell death, can cause inflammation and damage to surrounding cells.

Why does the cell explode during Necrosis?

The plasma membrane is damaged and ruptures, therefore the cell explodes and contents are released.

What causes Necrosis?

Caused by physical damage, toxins, pathogens, lack of oxygen.

Apoptosis vs Necrosis

* In necrosis, external factors cause internal tissue damage and cell disfunction.
* Apoptosis is pre-planned, and required for smooth bodily functioning..
* Necrosis is cellular death when exposed to extreme conditions.

Apoptotic Pathways

* Mitochondrial Pathway (Intracellular): Triggered when cell components, DNA, is damaged. Proteins signal for beginning of cascade reactions.
* Death Receptor Pathway (Extracellular): Triggered by immune cells outside the target cell. Cells under stress can all trigger this pathway.

Malfunctions in Apoptosis

* Too much apoptosis can lead to degenerative diseases such as Alzheimer’s or Parkinson’s.
* Too little apoptosis is seen in Syndactyly, where the skin between digits is not removed during embryonic development.

How can Apoptosis cause Cancer?

Due to apoptosis not occurring when it should:

* Genetic mutations that increase cell division rate.
* Caspases mutations that prevent function.
* Defects in proteins leading to caspases activation
* Defects in signal reception of apoptosis triggers.

Cascade

Series of caspases reactions.