Cell Cycle

Question 1

Interphase

Answer 1

95% of cell Cycle spent here
G1 + G2 + S
Chromosomes are decondensed
Cell growth and DNA replication (S phase)

Question 2

Phases

Answer 2

G0 = resting phase senescence 
G1 = cell grows in size (metabolically active) 
S = replicates DNA (synthesis) 
G2 = cell grows in size (prepares for mitosis)

Question 3

M phase

Answer 3

Mitosis
Nuclear division and cell duplication 
Most dramatic stage 
Separation of chromosomes 
Cytokenisis

Question 4

Cell Cycle checkpoints

Answer 4

Prevent entry into next phase
Ensures coordinated sequential events
Checks and balances before proceedings

Restrictions
-G1 to S: appropriate growth factors in the environment

DNA damage checkpoint
-G2 to M: all DNA is duplicated and correct

Spindle assembly checkpoint:
- mitosis (metaphase => anaphase) proper chromosome attachment and alignment

Question 5

Maturation promoting factor (MPF)

Answer 5

Cdk1/cyclin B

CDK= cyclin dependent kinase

Question 6

Cyclin D

Answer 6

Sysnthesis of cyclin D is initiated during G1 and drives the G1/S phase transition

Question 7

Cyclin E

Answer 7

Cyclin E binds to G1 phase Cdk2 which is required for the transition from G1 to S phase that determines DNA duplication
The cyclin E/CDK2 complex phosphorylates p27 (an inhibitor of cyclin D), tagging it for degradation which promotes expression of cyclin A, allowing for progression to S phase

Question 8

Cyclin A

Answer 8

Only cyclin that regulates multiple steps of the cell Cycle. It activates CDK2 and CDK1
Cyclin A/CDK2 required for passing into S phase
Cyclin A/CDK1 required for entry into M phase

Question 9

Cyclin B

Answer 9

The mitotic cyclin
The amount of cyclin B (which binds to Cdk1) and the activity of the cyclin B-cdk complex rise through the cel cycle until mitosis where they fall abruptly due to degradation of cyclkn B called maturation promoting factor

Question 10

Regulation of Cdk-Cyclin activity

Answer 10

Ubiquitination by APC (anaphase-promoting complex): degrades cyclin not Cdk
Phosphorylation/dephosphorylation: wee 1 phosphorylation (inhibition), Cdc25 dephosphorylation (activation)

Cdk inhibitors: protein inhibitors p21/p27 direct inhibition

Question 11

Restriction point

Answer 11

Start of cell cycle proliferation, regulatory point at G1, regulated by growth factors, point of commitment for the cell.
Can send cells to G0
If growth factors are present cell goes past restriction point and if not then opposite and goes into G0

Question 12

Skin fibroblasts

Answer 12

Remain in G0
Damaged tissue
Platelet-derived growth factor
Released by blood platelets during clotting mechanism

Question 13

Cyclin D

Answer 13

Induced by growth factor stimulation
Ras/RAF/Mek/Erk/ pathway
Continuous synthesis as long as gf is present
Quickly degraded by anaphase promoting complex (APC)

Question 14

CDK4,6

Answer 14

Forms complexes with cyclin D

Phosphorylates protein retinoblastoma (pRb)

Question 15

Retinoblastoma

Answer 15

Tumor suppressor protein
RB binds/inhibits E2F (transcription factor)
Inhibits cell proliferation.
Inhibited (phosphorylated) by: G1-Cdk (Cdk 4,6/cyclin D) and G1/S-Cdk (Cdk2/cyclin E)
E2F: transcription factor stimulated expression of cyclin E
Cyclin E: complex with Cdk2 (G1/S-Cdk), Cdk2/cyclin E inhibits Rb, helps cells bypass restriction point, regulated by p27 in early G1
Dysregulation: defects in cyclin D/E regulation => cancer, increased cell proliferation.