Cell Division And Apoptosis

Question 1

Outline the cell division cycle

Answer 1

G1= gap 1
S= DNA synthesis
G2= gap 2
M= mitosis

Question 2

How long is the total cell division cycle and how long are S and M stages?

Answer 2

Total ~24 hours
S ~10-12 hours
M ~0.5-1 hour

Question 3

How does the early embryonic cell cycle differ?

Answer 3

No gap phases

Question 4

What is G0?

Answer 4

Specialised non growing state

Reversible exit from cell cycle

Question 5

How can we study the state of DNA in interphase?

Answer 5

1. Flow cytometry- fluorescent dye that binds to DNA. Signals are proportional to DNA content
2. Autoradiography of epithelial tissue after brief exposure to ^3H thymidine detects silver grains over a nucleus in S phase

Question 6

What are the two types of yeast?

Answer 6

Saccharomyces cerevisiae= budding yeast

Schizosaccharomyces pombe= fission yeast

Question 7

Why is yeast used to study cell division?

Answer 7

• Proteins involves highly conserved in yeast and mammals
• Genomes already sequenced
• Genetic analysis simplified as both can grow as haploids

Question 8

How does temperature affect the yeast mutant ts?

Answer 8

Permissive temp- protein works

Restrictive temp- doesn’t work

Question 9

How do kinases and phosphatase regulate proteins?

Answer 9

• Kinases add PO4 (serine, threonine, tyrosine)

* Phosphatases remove PO4

Question 10

What is MPF?

Answer 10

M-phase promoting factor

Question 11

What is the evidence for MPF?

Answer 11

1. Induces oocytes of Xenopus to enter meiosis
2. Fusing a mitotic and interphase cell causes interphase nucleus to enter mitosis- chromosomes condense, whether or not it has replicated its DNA

Question 12

What happens to cyclin levels during cell division?

Answer 12

Rise from start of interphase then drop suddenly after mitosis

Question 13

What are the 3 checkpoints during cell division?

Answer 13

1. Before S- big enough size? (+ environment) Cdk activated-> S, Cdk inactivated-> complete S
2. Before M- all DNA replicated? (+ size + environment) Cdk activated-> M
3. Before anaphase- all Chromosomes aligned? Cdk inactivated-> anaphase

Question 14

What is Cdk?

Answer 14

Cyclin dependant kinase

Question 15

What controls the activity of Cdk?

Answer 15

Abundance of cyclin B

Phosphatase catalyses phosphorylation between Cdk and cyclin B

Question 16

What three processes does organ and body size depend on and how are they regulated?

Answer 16

Cell division, growth and death

Regulated independently, within the cell, by programmes controlled by extracellular signalling molecules

Question 17

What are the types of cell signalling involving membrane-borne receptors?

Answer 17

1. Endocrine- hormones
2. Paracrine- local mediators
3. Neuronal- neurotransmitters
4. Contact-dependant- membrane bound signal molecules

Question 18

Which cells enter G0?

Answer 18

• Neurons and skeletal muscle- terminally in G0
• Liver- most enter but can return to G1 if organ damage
• Some lymphocytes- withdraw from and re-enter cell cycle throughout life

Question 19

Which cells grow but don’t divide?

Answer 19

Nerve cells
Fat cells
Oocytes prior to fertilisation

Question 20

Which cells divide but don’t grow?

Answer 20

Reticulocytes- certain red blood cell- divide 5 times with little growth

Question 21

Describe cell necrosis

Answer 21

• Membrane ruptures, contents released

* Inflammatory response, nucleus appears flocculant

Question 22

Describe apoptosis

Answer 22

• Membrane blebs and cell shrinks
• No inflammatory response, nucleus condenses

Cell death is default state of all somatic cells- die unless otherwise prevented

Question 23

Describe apoptosis in relation to nerve cells

Answer 23

Cell death matches the number of nerve cells to target cells

Surviving target cells release survival factors to nerve cells

Question 24

What problems can apoptosis inhibition cause?

Answer 24

• Cancer- follicular lymphomas, carcinomas with p53 mutations, hormone dependant- breast, prostate, ovarian
• Autoimmune disorders- systemic lupus erythamatosus, immune mediated glomerulonephritis
• Viral- herpes, pox, Adeno

Question 25

What problems can apoptosis increase cause?

Answer 25

• AIDS
• Neurodegenerative disorders
• Myelodysplastic syndrome- aplastic anaemia
• Ischemic injury- stroke, myocardial infarction
• Toxin induced liver disease- alcohol

Question 26

What causes inhalatory anthrax?

Answer 26

Bacillus Anthracis spores engulfed by alveolar macrophages induce macrophage apoptosis- paralyses non-specific immunity

Question 27

What causes amoebic dysentery?

Answer 27

Liver/brain abscess damage is caused by induction of apoptosis in host cells by invading amoebae

Question 28

Outline the mechanism of apoptosis

Answer 28

• Internal self-digestion by CASPASE enzymes and endonucleases (cysteine at active site, cleaves at aspartate residue)
• requires activation of PROCASPASEs
• once activated, cannot be stopped

Question 29

What are the different apoptosis pathways?

Answer 29

Intrinsic:
default death (no GF)
stress activated

Extrinsic:
Instructed- Ligands bind to receptor

Question 30

What is the Caspase cascade?

Answer 30

->One molecule caspase X
-> Many caspase Y
Cleavage of cytosolic protein
-> More caspase Z
Cleavage of nuclear lamin

Question 31

Outline the intrinsic apoptosis pathway

Answer 31

1. Cytochrome c released from damaged mitochondria
2. Binds to Apaf-1
3. Procaspase-9 also binds
4. -> Apoptosome causes autocatalysis
5. -> Caspase cascade

Question 32

Outline the extrinsic apoptosis pathway

Answer 32

1. Fas ligand on killer lymphocyte binds to cell
2. Apaf-1 and procaspase-9 bind and form apoptosome
3. Caspase cascade is catalysed