Cell Cycle, Proliferation, Apoptosis

Question 1

What happens during G1?

Answer 1

Cell growth and contents duplication.

Question 2

What are the two main classes of regulatory molecules in G1?

Answer 2

Cyclins and cyclin-dependant kinases.

Question 3

Describe the biochemical pathway that leads to G1/S transition.

Answer 3

Cyclin D produced
Cyclin D binds to CDK4
Cyclin E gene transcribed
Cyclin E binds to CDK2
CyclinE-CDK complex prepares cells for G1/S transition
Increase in factors that promote S phase cyclin and DNA synthesis
Decrease in molecule inhibiting S phase

Question 4

What happens during S?

Answer 4

DNA replication, synthesis of DNA proteins, chromosome formation, joined by centromeres.

Question 5

How is the S phase controlled?

Answer 5

Active S cyclin-CDK complexes phosphorylate proteins that make up the pre-replication complexes on DNA replication origins. One complex at each origin for one replication only.

Question 6

What happens during G2?

Answer 6

Preparation for Mitosis.

Question 7

During what stage of the cycle is DNA condensation most extreme and a karyotype is obtained?

Answer 7

Metaphase.

Question 8

What happens in late prophase?

Answer 8

Nuclear envelope disappears
Nucleoli disappear
Spindle apparatus forms in the cytoplasm.

Question 9

During what stage of the mitosis does spindles attach to centromeres?

Answer 9

Metaphase

Question 10

What are the major molecules that regulate the cell cycle?

Answer 10

Rb, p53 and CDK to some extent.

Question 11

What is the function of Rb?

Answer 11

In its dephosphorylated state it prevents entry into S phase

Question 12

What is the effect of Rb phosphorylation?

Answer 12

Inactivation of Rb and S phase.

Question 13

What disease results from homozygous Rb mutation?

Answer 13

Retinoblastoma and 6x increased risk for other cancers.

Question 14

Is retinoblastoma recessive or dominant?

Answer 14

Recessive (need to be homozygous for disorder).

Question 15

What is retinoblastoma?

Answer 15

Tumour in retina

Question 16

What is the function of p53?

Answer 16

Activates transcription of inhibitors of the CDK/cyclin kinases to block G1/S transition. Critical apoptosis component.

Question 17

What percentage of tumours contain a p53 mutation?

Answer 17

> 50%

p53 can start or contribute to cancers.

Question 18

Name a gene critical for apoptosis.

Answer 18

Caspase 9

Question 19

What intracellular signals can lead to apoptosis?

Answer 19

DNA damage, changes in intracellular calcium.

Question 20

List the 6 steps of apoptosis.

Answer 20

Cell shrinkage
Cytoplasm density increases
Pyknosis
Karyorrhexis 
Blebbing 
Apoptotic body formation.

Question 21

Describe step 1 of apoptosis.

Answer 21

Cell shrinkage and rounding occurs through caspase-mediated breakdown of the cytoskeleton.

Question 22

Describe step 2 of apoptosis.

Answer 22

Cytoplasmic density increases, tight packing of organelles.

Question 23

Describe step 3 of apoptosis.

Answer 23

Pyknosis: condensation and localisation chromatin to the nuclear envelope.

Question 24

Describe step 4 of apoptosis.

Answer 24

Karyorrhexis: DNA in the nuclear envelope is fragmented and the nuclear membrane is broken down.

Question 25

Describe step 5 of apoptosis.

Answer 25

Blebbing of the cell membrane.

Question 26

Describe step 6 of apoptosis.

Answer 26

Cell is broken down into apoptotic bodies, which are phagocytosed.

Question 27

How can one determine if the rate of apoptosis is high?

Answer 27

Run PCR of produced DNA fragments.

Question 28

What causes necrosis?

Answer 28

Factors external to the cell or tissue.