Cell Cycle (Lec 8)

Question 1

Eukaryotic Cell Cycle

Answer 1

Interphase - period between cell divisons
- cell grows, develops, and prepares for division

M Phase - mitosis
- process of nuclear division and cytokinesis

Question 2

Cell Cycle Summary

Answer 2

G1: Gap phase between birth of new cell (M) and chromosome replication (S) − cell grows in preparation for the next mitosis

S: Synthesis phase − DNA is replicated to make an identical copy of each chromosome known as sister chromatids (4n in diploids; 2n in haploids)

G2: 2nd Gap phase − cell prepares for mitosis

M: Mitosis − cell segregates one copy of each chromosome into each new daughter cell

Question 3

G0 Phase

Answer 3

Cells may stay in G0 for an extended period, or even indefinitely.

Question 4

Centrosomes

Answer 4

Produce centrioles. One centrosome per cell in interphase

Question 5

Kinetochores

Answer 5

Microtubule binding structure, one per chromatid

Question 6

Cell Cycle Checkpoints

Answer 6

1. R-restriction point (external checkpoint-late G1)
   Where the CC becomes independent of mitogens. Regulated by growth factors, environment, oxygen (eg, if conditions are unfavourable, CC will arrest)
2. After S phase-internal checkpoint (G2)
   Monitors whether DNA replication is complete & if DNA damage has been repaired. Mitosis will not proceed if the cell ‘fails’.
3. During mitosis (Metaphase)
   Identifies whether chromosomes correctly attached to spindles & spindles formed properly.

Question 7

Checkpoints Ensure That…

Answer 7

1. Chromosomes are present
2. That critical stages of the cell cycle are completed before the next stage begins
3. Entry into S or M is prevented if the DNA is damaged
4. The spindles are properly formed & the chromosomes are properly attached
5. Cellular environment is favourable

Question 8

CDK-Cyclin Complexes

Answer 8

Sequential activation of different CDK-cyclin complexes controls cell cycle progression. Composed of 2 subunits:
1. Cyclin
– Present only in specific phase of cell cycle
– unstable, resulting in transient activity

2. Cyclin-Dependent protein Kinase (CDK)
   – substrate specificity & phosphorylation activity controlled by bound cyclin

Question 9

Cell Regulation

Answer 9

Going to the next step in the cycle requires activation of genes whose protein products are necessary for the next phase.

Question 10

Cell Cycle Control: Mitogens

Answer 10

Extracellular growth factors (mitogens) induce synthesis of cyclins

Question 11

CDK Targets

Answer 11

Phosphorylation initiates a chain of events =>
− Activation of specific transcription factors (TFs)
− TFs promote transcription of certain genes whose products are required for the next stage of the cell cycle

Question 12

p53 and p21: Damaged DNA

Answer 12

1. p53 recognises DNA damage, then activates protein p21
2. p21 binds to Cdk2-cyclinA complex, inhibits protein kinase activity
3. Cdk2-cyclinA complex can no longer phosphorylate Rb
4. Cell cycle is unable to progress from G1 -> S blocked

Question 13

p53 and p21: Repaired DNA

Answer 13

1. Once DNA is repaired, p53 levels drop,
2. p21 levels consequently fall and
3. Cdk2-cylinA no longer inhibited by p21
4. G1 -> S block is removed AND cell cycle proceeds

Question 14

p53: Tumour Suppressor Protein

Answer 14

If DNA damage is extensive, p53 activates genes (e.g. Puma) that lead to apoptosis, which prevents accumulation of multiple mutations that might result in development of cancer. p53 is most commonly mutated gene in ALL cancers