Week 5

Question 1

Explain what cyclins are and how they influence the progression through the cell.

Answer 1

a. Cyclins are proteins in the cytoplasm which fluctuate in concentration during the cell cycle.
i. Increased concentration prior to mitosis.
ii. Decrease in concentration after mitosis.
b. Cyclins drive the cell cycle once adhered to cyclin-dependent kinases. This allows activation of cyclin-dependent kinases, making them functioning enzymes which can target and phosphorylate proteins.
i. These target proteins regulate passage through the check points S, G1 and the early events of mitosis.

Question 2

How can cyclins become maturated to result in disease states?

Answer 2

2 mechanisms = loss of function or gain of function mutations.

Loss of function - could mean complete loss of or reduced function.
Gain of function - could mean extreme or small gain of function.

Use examples !!
CDK1
CDKA
Retinoblastoma

Question 3

Explain the principle of synthetic lethality and how this can be exploited for potential therapies.

Answer 3

a. Synthetic legality describes a situation in which mutations in two genes (gene couplets) together result in cellular death, but a mutation in either gene alone does not.
i. Applies that gene couplets compensate for eachother and are non-essential in their own right.
ii. Gene couplets have conditional essentiality. Neither gene is essential, expect in the event that one gene is mutation. This makes the other gene essential.
b. This arises when a combination of deficiencies in the expression of two or more genes leads to cell death. These deficiencies can arise through mutations, epigenetic alterations or inhibition of genes.

Give examples !!!! BRCA 1 (Usually repairs double strand breaks)
- This is subject to mutations and leads to a lot of breast cancer cases.
If you could target another protein which deals with double strand breaks, this could help resolve the mutations.
This gives a protein to target for therapy.
Will not affect healthy cells because they have functioning BRCA gene.

Specific therapies !! - Specific for one protein or gene mutation.