Cell Cycle

Question 1

What is the cell cycle?

Answer 1

The cell cycle is a series of events which ends in 2 daughter cells with identical diploid chromosomes.

Question 2

What is quiescence?

Answer 2

A state in which cells are not dividing.

Also known as G0

Question 3

Name the stages of mitosis.

Answer 3

1. Prophase
2. Prometaphase
3. Metaphase
4. Anaphase
5. Telophase

PPMAT

Question 4

What happens during prophase?

Answer 4

• Chromatin condensation
• Nucleolus disappears
• Centrioles move to poles

Question 5

What happens during prometaphase?

Answer 5

• Nuclear membrane dissolves

- Chromosomes attach to microtubules and start moving

Question 6

What happens during metaphase?

Answer 6

• Spindle fibres align the chromosomes along the middle of the cell nucleus (metaphase plate)

Question 7

What happen during anaphase?

Answer 7

• Paired chromosomes separate and move to opposite sides of the cell

Question 8

What happens during telophase?

Answer 8

• Chromatids arrive at opposite poles of the cell
• New membranes form around daughter nuclei
• Chromosomes decondense
• Spindle fibres disperse

Question 9

What are the stages of the cell cycle?

Answer 9

1. G1
2. S
3. G2
4. M

OR

Interphase and M phase

Question 10

What happens during G1?

Answer 10

• Monitor external environment (mitogen dependent)
• Cells grow in size and prepare to undergo DNA synthesis
• Commitment to divide

Question 11

What happens during S?

Answer 11

Synthesis of DNA

Question 12

What happens during G2?

Answer 12

• Cells grow in size
• Duplication of organelles
• Preparing for mitosis

Question 13

What happens during M?

Answer 13

• Mitosis (PPMAT)

- Cleavage of cell to produce daughter cells

Question 14

What are CDKs?

Answer 14

Cyclin-dependent kinases:

- they regulate progression through the cell cycle
- they are made up of serine/threonine kinases
- their activity is tightly regulated by cycling, CKIs and phosphorylation/dephosphorylation

Question 15

What are cyclins?

Answer 15

• Activator proteins that are up or down regulated depending on the phase of the cell cycle
• Unstable proteins
• Different cyclins are associated with different CDKs

Question 16

What is MPF?

Answer 16

Maturation Promoting Factor:

- also known as CDK1-cyclin B 
- necessary for progression to stage M 
- nuclear envelope destroyed 
- chromosome condensation 
- spindle formation

Question 17

What are CKIs?

Answer 17

Cyclin-dependent kinase inhibitors:

- small proteins that block cyclin/CDKS activity
- inhibit either by forming an inactive complex or acting as a competitive CDK ligand

Question 18

What are the three families of CKIs?

Answer 18

• p21 CIP
• p27 KIP
• p16 INK

Question 19

What is the restriction point in the cell cycle?

Answer 19

The point in G1 at which the cell becomes committed to the cell cycle:

- determined by external factors and signals
- cyclin D pairs with CDK 4/6 to regulate this

Question 20

What are checkpoints in the cell cycle?

Answer 20

Cell monitoring:

- favourable external environment (presence of growth factors)
- favourable internal environment (sufficient growth) 
- DNA damage
- replication errors
- spindle attachment
- chromosome integrity

Question 21

What are 4 checkpoints of the cell cycle?

Answer 21

1. Restriction point (G1)
   2/3. DNA damage (G1 and G2)
2. Metaphase checkpoint (M)

Question 22

Discuss the restriction point

Answer 22

• determines if conditions are favourable to proceed
• irreversibly commits to the cell division process
• external influences (e.g. growth factors) are important in passing this checkpoint:
  - sufficient signal —> cell cycle progresses
  - insufficient signal —> cell cycle arrests
• cell will only pass this checkpoint if it is an appropriate size and has enough energy reserves
• dependent on the accumulation of cyclin D
• occurs 2-3 hours before S phase
• retinoblastoma (RB) acts as a gatekeeper

Question 23

What are some examples of growth factors and their function?

Answer 23

1. Epidermal growth factor (EGF) - re-epithelialisation (keratinocyte proliferation and migration)
2. Platelet-derived growth factor (PDGF) - matrix formation ( increased numbers and activity of fibroblasts) / remodelling (production of proteases)
3. Vascular endothelial growth factor (VEGF) - angiogenesis (endothelial cell proliferation and migration)

Question 24

What is retinoblastoma (RB)?

Answer 24

• tumour suppressor protein
• monitors cell size
• RB binds to transcription factor (e.g. E2F) to inhibit proteins being assembled which would allow cell cycle to progress to S stage
• As the cell size increases RB is phosphorylated until it reaches the point of inactivation, releases the E2F which can then turn on the gene which will produce the transition proteins

Question 25

Discuss the DNA damage checkpoint

Answer 25

- checks for chemical mutagens, radiation, errors in replication - happens late G1 and late G2 (so before DNA in synthesis and before cell division occurs) - p53 may be involved to help repair DNA or trigger apoptosis - p21 may also be involved to halt the cycle and inhibit the activity of the CDK/cyclin complex - G2 checkpoint ensures all chromosomes have been accurately replicated before mitosis

Question 26

What is p53?

Answer 26

- transcription factor - can halt cell cycle (p21) and recruit enzymes to repair DNA damage - can induce apoptosis if DNA cannot be repaired

Question 27

What does p21 do?

Answer 27

- halts the cell cycle by binding to and inhibiting the activity of the CDK/cyclin complex

Question 28

Discuss the spindle (M) checkpoint

Answer 28

- takes place near the end of metaphase - determines whether all the sister chromatids are correctly attached to the spindle microtubules - cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to at least 2 spindle fibres arising from the opposite poles of the cell - important as anaphase is irreversible - anaphase promoting complex (APC) is inhibited until all chromosomes are securely attached