cell cycle and apoptosis

Question 1

What is the frequency of cell division like? (Cycle time)

Answer 1

Embryo- 20 mins
Skin- 12-24hrs
Liver- years

Question 2

What is mitosis?

Answer 2

Results in 2 identical daughter cells

DNA duplicated exactly and divided equally

Question 3

What is the cell cycle?

Answer 3

Mitotic phase (cell division)
Interphase-
~ Gap1- cell grows
~ S- replication of DNA
~ Gap2- cell prepares to divide

GO- cells that cease division

Question 4

What are the stages of mitosis?

Answer 4

Interphase

Prophase- condensation of DNA into chromosomes and attach to spindle structure (microtubules)

Prometaphase- nuclear envelope breaks down

Metaphase- chromosomes lined up in an equatorial plate

Anaphase- tension applied to chromosomes (molecular motors) pull them apart to opposite poles

Telophase- cells separate (contractile actin ring)- cytokinesis

Question 5

How is the cell cycle regulated?

Answer 5

Extra and intracellular signals influence
Checkpoints at different stages
~critical points- G1, G2 and M phase

G1- checks environment is right, enough nutrients, no damage etc
G2- complete replication correct
M- alignment of chromosomes correct

Question 6

What is the nuclear fusion experiment (Rao and Johnson)?

Answer 6

Fuses nuclei together to see the influence of different phases on eachother

Conclusion- mitotic nuclei release mitosis-promoting factor that affects all interphase nuclei to drive it forward

Question 7

What are cyclins?

Answer 7

Proteins that control cell cycle

Levels rise and fall with differ t stages

Question 8

What are cyclin dependent kinases?

Answer 8

Phosphorylation proteins that control cell cycle
Levels fairly constant
CDK binds to appropriate cyclin
Activity controlled by cyclin dependent kinase inhibitors

Question 9

What regulates the cell cycle?

Answer 9

Cyclin and CDK synthesis
Cyclin degradation, CDK phosphorylation, CDK inhibition

Promoting factor= Cyclin + CDK
~phosphorylates and activates proteins inv in chromatin condensation, nuclear envelope breakdown, spindle assembly and own destruction

Question 10

What is MPF?

Answer 10

Mitosis promoting factor

At G2/M checkpoint

Question 11

What is APC?

Answer 11

Anaphase promoting complex
Degraded cyclin B
At spindle checkpoint

Question 12

How might extracellular signals promote cell division?

Answer 12

Growth factor binds to cell surface receptor
Changes conformation slightly
Activates protein kinase cascade
Translocated to nucleus
Binds to DNA and promotes transcription, translation OR cyclin dependent kinase
Cell division

Question 13

What is G0?

Answer 13

Cells permanently/temporarily leave cell cycle
Most cells in G0
Resting or quiescent
Can do other things eg. secrete
~Terminal differentiation- permanent eg. Keratinocytes, lymphocytes
~Cells that can re-enter cycle- in response to signals eg. Liver

Question 14

What is cell cycle in disease?

Answer 14

Dysregulated cell growth- cancer
Many cell cycle regulatory genes are TSGs

Cancer treatments target rapidly growing cells-
~high energy radiation
~chemotherapy targets DNA replication, mitosis and cytokinesis (drugs prevent formation of new blood vessels)

Question 15

What is the p53 TSG?

Answer 15

Guardian of genome
If DNA damaged, p53-
~initiate DNA repair
~arrest cell cycle
~initiate apoptosis

p53 is mutated in 50% cancers

Defective p53 allows abnormal cells to proliferate

Question 16

How can the cell cycle be used in oral pathology?

Answer 16

Mitosis visible under haematoxylin and eosin

Number- indicates active growth eg. Ulcer healing

Location- eg. Suprabasal may indicate pathology

Question 17

What do apoptosis?

Answer 17

Programmed cell death
Essential- normal development
Destroys cells that are threat (virus infected, immune, DNA damage)
Initiated by withdraw of positive signals (eg growth factors) or receipt of negative signals (eg UV)

Question 18

How does apoptosis happen?

Answer 18

Cells shrink slightly
Nuclear breakdown into fragments
Cell breaks down into smaller membrane bound remains
These are phagocytosed

Question 19

What is the difference between apoptosis and necrosis?

Answer 19

Apoptosis- controlled, energy dependent, cells shrink, membrane intact, non-inflam, no scarring, small cell groups, nuclear fragmentation

Necrosis- uncontrolled, no ATP required, cell swells, no membrane integrity, inflam, scarring, large cell group, nuclear dissolution, pathological

Question 20

What is intrinsic apoptosis?

Answer 20

Controlled by integrity of mitochondrial membrane

If not there, cytochrome C is released* into cytoplasm and combines w other protein
Activates- cascade of caspase activation

Bcl-2 (b cell lymphoma) stops this formation*

Question 21

What is extrinsic apoptosis?

Answer 21

Ligand (eg. FasL) binds to cell surface receptor (eg. Fas)
This combined w adaptor molecules (eg. FADD)
Activates- cascade of caspase activation

Question 22

What are caspases?

Answer 22

Proteolytic enzymes (cysteine proteases)
Effectors of apoptosis
Present as inactive proenzyme (zymogen)
Activation cascade (caspase 9 activates caspase 2,3,6,7,8,10)
Numerous substrates (eg. Cytoskeleton, nuclear membrane)

Question 23

What is apoptosis in disease?

Answer 23

Avoidance in cancer eg. Bcl-2
HPV inactivates p53
EBV produce protein similar to Bcl-2
Melanoma inhibits expression of Apaf-1
Fas antagonist- block T cell cytotoxicity
Autoimmune- increase apoptosis eg. Rheumatoid arthritis
Increase in apoptosis eg. Neurodegenerative

Question 24

What is apoptosis in oral pathology?

Answer 24

Apoptotic bodies/cells under H&E

Eg. Lichen planus