Cell cycle and apoptosis

Question 1

Mitosis and cell cycle lead to

Answer 1

Cell growth and division (mitosis)

Production of two identical daughter cells, with DNA duplicated exactly and divided equally

Question 2

Cell cycle

Answer 2

Ordered set of events
Interphase (longest phase) –> mitotic phase –> G0 (cells that cease division) –> G1 (cell grows) –> S phase (replication of DNA)

Question 3

Mitosis and cell cycle are essential

Answer 3

Even in mature organisms

Question 4

Mitosis

Answer 4

Interphase –> prophase (kineticores) –> metaphase –> anaphase –> telophase

Question 5

Regulation of cell cycle

Answer 5

Extra- and intracellular signals
G1 checkpoint - growth and environment, DNA damage
G2 checkpoint - DNA daage
M checkpoint - chromosome alignment on spindle

Question 6

Rao and Johnson Nuclear Fusion Expt

Answer 6

S + G1 –> 2S (S phase nucleus releases something that drives G1 nucleus into S)
S + G2 –> S + G2 (G2 nucleus is resistant to S phase promoting factor)
G1 + G2 –> G1 + G2 (G1 and G2 do not influence each other)
Interphase + M –> 2M (mitotic nuclei release mitosis-promoting factor that affects all interphase nuclei)

Question 7

Cell cycle control

Answer 7

Cyclins:

• G1 cyclin (D)
• S-phase (E & A)
• M-phase (B & A)
• Levels rise and fall with stages of the cell cycle (D remains constantly high)

Question 8

Cyclin dependent kinases (Cdks)

Answer 8

Trigger major cell cycle transitions
Phophorylate proteins that control cell cycle
Levels remain fairly constant
Must appropriate cyclin to be activated
Activity control by Cdk inhibitors
-certain cdks bind to certain kinases at diff stages of cell cycle

Question 9

MPF

Answer 9

Mitosis promoting factor initiates mitosis
Mitotic cyclins destroyed
activates anaphase promoting factor and chromatids separate (M)

Question 10

G1 cyclins

Answer 10

bind to cdks and prepare chromosomes for replication

Question 11

SPF

Answer 11

S phase promoting factor enters nucleus and prepares DNA for replication

Question 12

When is cyclin E destroyed

Answer 12

After S phase

Question 13

When does mitotic cyclin conc. increase

Answer 13

G2 phase

Question 14

G0

Answer 14

‘Quiescent’
Cells that have permanently or temporarily left cell cycle e.g. lymphcyte
Terminal differentiation e.g. neuron, epithelial cell
Active repression of genes needed for cell cycle

Question 15

Cell cycle in disease

Answer 15

Dysregulated cell growth = cancer

Many cell cycle regulatory genes are tumour suppressor genes

Question 16

p53

Answer 16

Blocks cell cycle if DNA damaged

Mutated in approx. 50% of cancers

Question 17

p27

Answer 17

Cyclin dependent kinase inhibitor

< levels predict poor outcome in breast cancer

Question 18

Cell cycle in oral pathology

Answer 18

Mtosis visible in H&E
Number indicated active growth e.g. ulcer healing
Location e.g. suprabasal may indicate pathology

Question 19

Apoptosis

Answer 19

Programmed cell death
Essential for normal development
Destroys cells that may be threat (virus infected, immune, DNA damage)
Withdraw of positive signals (growth factors, hormones)
Receipt of negative signals (e.g. UV, death activators, hypoxia)

Question 20

Apoptosis vs necrosis

Answer 20

controlled/ uncontrolled
energy dependent / no ATP required
cells shrink/ swell
membrane intact / no membrane integrity
non-inflammatory/ inflammatory
no scarring/ scarring
individual or small cell groups / large cell groups
nuclear fragmentation/ nuclear dissoloution
physiological (can be pathological)/ pathological

Question 21

2 main pathways of inducers and pathways

Answer 21

Intrinsic: mitochondrion and cytochrome c
-if cyt c released, combines with apaf-1 –> cascade –> apoptosis
-bcl-2 protein binds to apaf-1 –> stops it initiating apoptosis
-tumour associated cells might block pathway
Extrinsic: ligand binds to death receptor
-conformational change initiates cascade –> apoptosis
-e.g. cytotocis T cells kills other cells this way

Question 22

Caspases

Answer 22

Proteolytic enzymes (cysteine proteases)
Effectors of apoptosis
Present as inactive proenzymes (zymogen)
Activity controlled by number of mechanisms

Question 23

Caspase activation cascade

Answer 23

Caspase 9 activates caspase 2, 3, 6, 7, 8, 10

Question 24

Capsase substates

Answer 24

Cytoskeleton
Nuclear membrane
Activation of DNase
Bcl-2

Question 25

Apoptosis in dental physiology

Answer 25

Craniofacial growth & development
Homeostasis in mucosa, skin and pulp
Tooth development
Bone remodelling (osteoblasts die by apop.)
Wound healing (inflammatory cells)

Question 26

Apoptosis in disease

Answer 26

Avoidance in cancer = survival/ proliferation
HPV inactivates p53
Epstein Barr Virus protein similar to Bcl-2
Melanoma inhibits expression of Apaf-1)
Fas antagonists block T cell cytoxicity
Autoimmune e.g. SLE (lupus), rheumatoid arthritis

Question 27

Apoptosis in disease: increase in apoptosis

Answer 27

Neurodegenerative, HIV

Question 28

Apoptosis in oral cancer and salivary gland tumours

Answer 28

Bcl-2, fas. p53 differentially expressed

Question 29

Apoptosis in lymphomas

Answer 29

Reduced apoptosis

Question 30

Apoptosis in odontogenic tumours and cysts

Answer 30

Active expression of apoptotic proteins by lining

Question 31

Apoptosis in Sjogren’s syndrome

Answer 31

Epithelium sensitive to apoptosis

Question 32

Apoptosis in oral pathology

Answer 32

Apoptotic bodies/ cells visible under H&E (tend to pull away from other cells due to shrinkage)
-highly eosinophilic due to high conc. of enzymes
Common conditions such as Lichen Planus