tumour pathology 4

Question 1

what is a cell cycle?

Answer 1

the interval between mitotic divisions

Question 2

what are the phases of the cell cycle, and what happens in each?

Answer 2

1. G1 - synthesis of components required for DNA synthesis
2. S - DNA synthesis
3. G2 -preparation for mitosis
4. M - mitosis and cell division

G0- extension of G1, quiescent state, dormant

Question 3

when does DNA repair occur?

Answer 3

G2 phase

Question 4

when can the cell cycle be affected by external factors?

Answer 4

in the G1 phase

Question 5

examples of external factors

Answer 5

hormones, cytokines, growth factors, stroma

Question 6

where are the checkpoints of the cell cycle?

Answer 6

• G1 checkpoint at the G1/S transition
• G2 checkpoint at -the G2/M transition
• M checkpoint between metaphase and anaphase

Question 7

where is the cell cycle arrested if cell size is inadequate?

Answer 7

G1 or G2

Question 8

where is the cell cycle arrested if nutrient supply is inadequate?

Answer 8

G1

Question 9

where is the cell cycle arrested if essential external stimuli are lacking?

Answer 9

G1

Question 10

where is the cell cycle arrested if DNA is not replicated?

Answer 10

S

Question 11

where is the cell cycle arrested if DNA is damaged?

Answer 11

G1 or G2

Question 12

where is the cell cycle arrested if chromosomes mis-align

Answer 12

M-phase

Question 13

how do checkpoints work?

Answer 13

1. cyclin dependent kinases are present in the cell
2. cyclin levels rise if the checkpoint has the go-ahead.
3. these bind to CDKs, activating them.
4. the active CDKs then act by phosphorylating sybstrates
5. these phosphorylated substrates are required for the next stage of the cell cycle

the cell cycle is also regulated using CDK inhibitors

Question 14

what does INK4A inhibit?

Answer 14

CDK4

Question 15

INK4A inhibitors

Answer 15

p16^INK4A
p15^INK4B
p18^INK4C
p19^INK4D

Question 16

CIP/KIP inhibitors

Answer 16

p21^CIP1

Question 17

what does the retinoblastoma gene encode for?

Answer 17

pRb

Question 18

when is pRb active?

Answer 18

when it is hypophosphorylated

Question 19

when is pRb inactive?

Answer 19

when it has been phosphorylated by cyclin D/CDK complexes

Question 20

what is the function of pRb?

Answer 20

E2F transcription factor, this activates vital target genes for the stimulation of cell cycle entry

Question 21

how do oxidising and alkylating agents cause carcinogenesis?

Answer 21

they critically damage purine and pyrimidine bases in DNA

Question 22

what is a DNA adduct?

Answer 22

covalently bound products of DNA and a chemical carcinogen

Question 23

how does radiation damage DNA?

Answer 23

damages the purine and pyrimidine bases

Question 24

types of ionising radiation

Answer 24

• UV (UV-B in sunlight)
• X-rays
• Gamma radiation

Question 25

what are the two regulatory pathways regularly disrupted to cause cancer?

Answer 25

1. The cyclin D-pRb-E2F pathway

2. p53 pathway

Question 26

which checkpoint is usually dysregulated in cancer cells and which four genes are mutated?

Answer 26

G1/S checkpoint

Rb, CDK4, cyclin D and p16

Question 27

p53 function

Answer 27

maintains genomic integrity.

does this by inducing cell cycle arrest at G1 or facilitating DNA repair or inducing apoptosis if DNA damage is severe