Regulation of cell cycle and DNA replication

Question 1

What are the different stages of the cell cycle?

Answer 1

G1, S, G2, M

(This is the correct order!)

Question 2

Which CDK is associated with M-phase?

Answer 2

B-CDC2 Kinase

Question 3

Which CDK is associated with G1 phase?

Answer 3

D-CDK4/6 and E-CDK2

Question 4

Which CDK is associated with S phase?

Answer 4

A-CDK2

Question 5

Which CDK is associated with G2 phase?

Answer 5

A-CDC2

Question 6

What are the three main checkpoints in the cell cycle?

Answer 6

G1/S - Prepares the cells for synthesis. Differentiates, make DNA repairs.

inter-S - Controls the DNA during S-phase so that repairs can take place.

G2/M - Ensures that everything is in order before segregation. Emphasis on DNA repair.

Question 7

What defines cyclines?

Answer 7

Cyclines are expressed differentially during the cell cycle. They are all homologous and consist of two alpha folds (1 for CDK interactions, 1 for cycline degradation).

Question 8

What’s the relationship between cyclines and CDKs?

Answer 8

Cyclines generally activate the catalytic site of CDKs.

Cyclines vary throughout the cell cycle, CDKs don’t.

Question 9

Describe RAS-MAPK signaling.

Answer 9

Affects lots of cell cycle functions.

1. EGF binds its receptor (EGFR) + associated complex.
2. RAS gets phosphorylated, which in turn complexes with RAF.
3. RAF-RAS complex phosphorylates MEK –> MAPK (ERK).

Question 10

Describe JAK-STAT signaling.

Answer 10

Signals regarding immunity, cell division, cell death, and tumor formation.

1. Cytokine receptors are present on the cell surface as dimers, it gets bound by various ligands such as cytokines. 1x JAK is bound IC to the cytokine receptors.
2. JAK phosphorylates the cytokine receptor upon cytokine binding.
3. JAK phosphorylates STAT which dimerizes.
4. STAT dimer enters the nucleus and binds promoters.

Question 11

Describe TGFb signaling.

Answer 11

1. TGFbR2 gets bound and catalyzes the phosphorylation of TGFbR1. Each ligand binds a specific receptor-sub type. For activation, 2x Type 1 and 2x Type 2 receptors need to aggregate.

Ligands
- TGFb 1-3
- BMPs
- Activiins

2. If the ligand is anything except BMPs, the intracellular signaling is mediated by SMAD2/3. If BMPs, SMAD1, 5, 8/9.

R-SMAD (SMAD1-3, 5, 8/9) and co-SMAD (SMAD4)

Question 12

What’s the purpose of CDK inhibitors? Give two examples of them.

Answer 12

CDK inhibitors are the mediators of cell cycle checkpoints.

CDKN1 encodes p21 and p27 which activate CDK4/6 and inhibit CDK2. (This is required to progress from G1 to S.

CDKN2A/B encodes p14 and p16 (via alternative splicing). P14 degrades MDM2, which is an inhibitor of p53. p16 inhibits CDK5/7.

p53 is the guardian of the genome, it’s central in apoptotic signals.

Question 13

What’s the importance of myc?

Answer 13

Myc is a net calculator of all proliferative signals. You’ll find it immediately downstream of the RAS-MAPK signaling pathway. It’s an important proto-onco gene.

Myc needs to bind Max to mediate proliferation. To do the opposite, it needs to bind Mad.

Question 13

What’s the importance of myc?

Answer 13

Myc is a net calculator of all proliferative signals. You’ll find it immediately downstream of the RAS-MAPK signaling pathway. It’s an important proto-onco gene.

Myc needs to bind Max to mediate proliferation. To do the opposite, it needs to bind Mad.