Cell Division And Apoptosis Flashcards
Outline the cell division cycle
G1= gap 1 S= DNA synthesis G2= gap 2 M= mitosis
How long is the total cell division cycle and how long are S and M stages?
Total ~24 hours
S ~10-12 hours
M ~0.5-1 hour
How does the early embryonic cell cycle differ?
No gap phases
What is G0?
Specialised non growing state
Reversible exit from cell cycle
How can we study the state of DNA in interphase?
- Flow cytometry- fluorescent dye that binds to DNA. Signals are proportional to DNA content
- Autoradiography of epithelial tissue after brief exposure to ^3H thymidine detects silver grains over a nucleus in S phase
What are the two types of yeast?
Saccharomyces cerevisiae= budding yeast
Schizosaccharomyces pombe= fission yeast
Why is yeast used to study cell division?
- Proteins involves highly conserved in yeast and mammals
- Genomes already sequenced
- Genetic analysis simplified as both can grow as haploids
How does temperature affect the yeast mutant ts?
Permissive temp- protein works
Restrictive temp- doesn’t work
How do kinases and phosphatase regulate proteins?
- Kinases add PO4 (serine, threonine, tyrosine)
* Phosphatases remove PO4
What is MPF?
M-phase promoting factor
What is the evidence for MPF?
- Induces oocytes of Xenopus to enter meiosis
- Fusing a mitotic and interphase cell causes interphase nucleus to enter mitosis- chromosomes condense, whether or not it has replicated its DNA
What happens to cyclin levels during cell division?
Rise from start of interphase then drop suddenly after mitosis
What are the 3 checkpoints during cell division?
- Before S- big enough size? (+ environment) Cdk activated-> S, Cdk inactivated-> complete S
- Before M- all DNA replicated? (+ size + environment) Cdk activated-> M
- Before anaphase- all Chromosomes aligned? Cdk inactivated-> anaphase
What is Cdk?
Cyclin dependant kinase
What controls the activity of Cdk?
Abundance of cyclin B
Phosphatase catalyses phosphorylation between Cdk and cyclin B
What three processes does organ and body size depend on and how are they regulated?
Cell division, growth and death
Regulated independently, within the cell, by programmes controlled by extracellular signalling molecules
What are the types of cell signalling involving membrane-borne receptors?
- Endocrine- hormones
- Paracrine- local mediators
- Neuronal- neurotransmitters
- Contact-dependant- membrane bound signal molecules
Which cells enter G0?
- 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
Which cells grow but don’t divide?
Nerve cells
Fat cells
Oocytes prior to fertilisation
Which cells divide but don’t grow?
Reticulocytes- certain red blood cell- divide 5 times with little growth
Describe cell necrosis
- Membrane ruptures, contents released
* Inflammatory response, nucleus appears flocculant
Describe apoptosis
- Membrane blebs and cell shrinks
- No inflammatory response, nucleus condenses
Cell death is default state of all somatic cells- die unless otherwise prevented
Describe apoptosis in relation to nerve cells
Cell death matches the number of nerve cells to target cells
Surviving target cells release survival factors to nerve cells
What problems can apoptosis inhibition cause?
- Cancer- follicular lymphomas, carcinomas with p53 mutations, hormone dependant- breast, prostate, ovarian
- Autoimmune disorders- systemic lupus erythamatosus, immune mediated glomerulonephritis
- Viral- herpes, pox, Adeno
What problems can apoptosis increase cause?
- AIDS
- Neurodegenerative disorders
- Myelodysplastic syndrome- aplastic anaemia
- Ischemic injury- stroke, myocardial infarction
- Toxin induced liver disease- alcohol
What causes inhalatory anthrax?
Bacillus Anthracis spores engulfed by alveolar macrophages induce macrophage apoptosis- paralyses non-specific immunity
What causes amoebic dysentery?
Liver/brain abscess damage is caused by induction of apoptosis in host cells by invading amoebae
Outline the mechanism of apoptosis
- 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
What are the different apoptosis pathways?
Intrinsic:
default death (no GF)
stress activated
Extrinsic:
Instructed- Ligands bind to receptor
What is the Caspase cascade?
->One molecule caspase X
-> Many caspase Y
Cleavage of cytosolic protein
-> More caspase Z
Cleavage of nuclear lamin
Outline the intrinsic apoptosis pathway
- Cytochrome c released from damaged mitochondria
- Binds to Apaf-1
- Procaspase-9 also binds
- -> Apoptosome causes autocatalysis
- -> Caspase cascade
Outline the extrinsic apoptosis pathway
- Fas ligand on killer lymphocyte binds to cell
- Apaf-1 and procaspase-9 bind and form apoptosome
- Caspase cascade is catalysed
