LC 3.6 Cell Cycle

Question 1

Cells which permanently leave the cell cycle are called what?
Give an example

Answer 1

Post-mitotic cells

Nerve cells

Question 2

Where are the cell cycle ‘checkpoints’?

Answer 2

• G1 –> S
  
  • S phase
  • G2–> M
  • Metaphase –> Anaphase

Question 3

What is checked at the metaphase-anaphase checkpoint?

Answer 3

Checks that DNA has moved properly into each daughter cell and that they have split properly

Question 4

Which complex is responsible for progression past the metaphase-anaphase checkpoint? What class of enzyme is this and what does it do?

Answer 4

Anaphase-promoting complex (APC)

A ubiquitin ligase

Degrades securin, which holds chromosomes together, allowing them to separate.

Question 5

Which enzymes drive the cell cycle and how do they work?

Answer 5

Cyclin dependent kinases (Cdks)

Need to bind to the correct cyclin to become active

cyclin-Cdk complex then triggers a cascade that allow the progression of the cascade

Question 6

Which cyclin-Cdk complexes are used in the cell cycle, and where?

Answer 6

In order:

G1
  •  Cyclin D - CDK4
  •  Cyclin D - CDK6
G1 --> S
  •  Cyclin E - CDK2
S checkpoint
  •  Cyclin A - CDK2
G2
  •  Cyclin A - CDK1
G2 --> M
  •  Cyclin B - CDK1

Question 7

Which cyclin remains high for majority of the cell cycle?

Answer 7

Cyclin D

Question 8

Which cyclin is highest during G2 phase?

Answer 8

Cyclin A

Question 9

Which molecules stimulate the cell cycle? When do they do this?

Give examples of these.

Answer 9

Mitogens, in response to injury, etc.

E.g:
• Platelet derived growth factor (PDGF)
• Fibroblast growth factor (FGF)

Question 10

How do mitogens act on the cell?

Answer 10

They stimulate G1/S cyclin activity (cyclin D and cyclin E production) through the MAP kinase pathway

Question 11

What is the MAP kinase pathway also known as?

What condition are many of the genes in this pathway linked to?

Answer 11

The mitogenic pathway/ERK

(mitogen activated protein = MAP)

Cancer

Question 12

A gene which under abnormal circumstances can cause a normal cell to become cancerous is called?

Answer 12

Oncogene

Question 13

Outline the mitogen - MAP kinase pathway.

Answer 13

• Mitogen binds to a receptor
  
  • Receptor activates the transducer Ras GTPase
  • A signalling cascade activates MAP kinase
  • This leads to the expression of ‘early genes’
  • MYC (a regulatory protein) is synthesised
  • MYC stimulates production of Cyclin D and Cyclin E

Question 14

What protein families inhibit Cdks? Outline which complexes are inhibited by each protein family

Answer 14

INK4 Family
• Cyclin D - CDK4 (in G1)

Cip/Kip Family
  •  Cyclin D - CDK6 (in G1) 
  •  Cyclin E - CDK2 (in G1-->S)
  •  Cyclin A - CDK2 (in S)
  •  Cyclin A - CDK1 (in G2)
  •  Cyclin B - CDK1 (in G2-->M)

Question 15

What proteins are found in each inhibiting enzyme family?

Answer 15

INK4
  •  p15
  •  p16
  •  p18
  •  p19

Cip/Kip
• p21
• p27
• p57

Question 16

Which protein is the tumour suppressor and how does it work?

Answer 16

p53:

Upregulates p21 activity to inhibit cyclin-CDK complexes

This leads to cell cycle arrest or apoptosis depending on if the damage can be repaired

Question 17

Name the processes of permanently and temporarily leaving the cell cycle.

Answer 17

Temporary - Creascence (can re-enter the cell cycle whenever needed like liver cells)

Permanent - Senescence (irreversible)

Question 18

What causes cellular senescence?

Answer 18

Inhibition of cell cycle by the INK4/Cip protein families in response to:
• Damage
• Reduced repair

Question 19

What phase do cells enter when undergoing senescence?

Answer 19

Irreversible G0 state

Question 20

What happens when telomeres become too short?

Answer 20

It is recognised as DNA damage, and so p53 arrests the cell cycle inducing cellular senescence