What is the cell cycle defined as?
The interval between mitotic divisions
What are the external factors that affect cell cycle control?
Hormones, growth factors, cytokines, stroma
When is the cell cycle dependant on external stimuli and when is it autonomous?
Prior to restriction point - external stimuli After restriction point - autonomous
Where do checkpoints in the cell cycle exist?
G1, G2 and metaphase
If the cell size is inadequate, which checkpoint will cease the cell cycle?
If the nutrient supply is inadequate, which checkpoint will cease the cell cycle?
If there is a lack of external stimulus, which checkpoint will cease the cell cycle?
If the DNA is not replicated, where will the cell cycle cease?
If DNA damage is detected, where will the cell cycle cease?
G1 or G2
If there is chromosome misalignment, where will the cell cycle cease?
What is the main purpose of the G1, G2 and M phase checkpoints?
G1 - Checks DNA integrity G2 - Checks proper chromosome duplication M - Assesses attachment of each kinetochore to a spindle fiber
What are the catalytic sub-units called and what are they activated by?
Cyclin dependant kinases Activated by a regulatory sub-units called cyclins
What is the name given to the active enzyme complex?
What is the effect of CDK/cyclin complexes?
Phosphorylate target proteins
What is the result of the CDK/cyclin complexes phosphorylating the target proteins?
Results in activation or inactivation of that substrate
What is the function of the substrates that are inactivated or activated by CDK/cyclin complexes?
Substrates regulate what happens in the next phase of the cell cycle
How are CDK's and cyclins regulated?
CDK's are constitutively expressed in an inactive form Cyclins accumulate and are destroyed as cycle progresses CDK inhibitors
What are the two methods of inhibition of the CDK inhibitors?
Bind to CDK and prevent the association of these CDK's with their cyclin regulatory proteins. They bind to the CDK/cyclin complexes
What is the function of the pRb phosphoprotein?
CDK/cyclin complexes phosphorylate this protein. Once phosphorylated it becomes inactive and loses affinity for the E2F transcription factor. This free E2f now activates vital target genes E2F is a potent stimulator of cell cycle entry
What are the environmental factors that can cause genetic damage?
Chemicals Radiation Oncogenic viruses
How do chemicals cause carcinogenesis?
Oxidising and alkylating agents damage bases. Carcinogens or their metabolites react with DNA forming DNA adducts. The formation of these covalently bound products at particular chromosome sites causes cancer.
What are the targets for radiation carcinogenesis?
Purine and pyrimidine bases
Which forms of high energy radiation are carcinogenic?
Ultraviolet radiation X rays Gamma radiation
Which genes mutate at G1-S to cause cancer?
Rb, CDK4, Cyclin D and p16
What is the function of P53?
Maintains genomic integrits
When do levels of p53 increase?
When the cell is damaged
What is the effect of increased levels of P53?
Cell cycle arrest at G1 Facilitates DNA repair Apoptosis
What is the effect of a mutated P53 gene?
No G1 arrest or repair of DNA
•Genetically damaged cells proliferate and form malignant neoplasms