cell cycle, quiescence and senescence in eukaryotes

Question 1

free living cell growth mainly determined by

Answer 1

environ cues eg nutrient supply

Question 2

In multicellular animals cell growth mainly controlled by

Answer 2

Extracellular signals (from cells around them)

Question 3

Other processes cells can undergo except for growth/proliferation

Answer 3

stop proliferating
Undergo apoptosis (planned cell  death)
Undergo Necrosis (planned cell death

Question 4

focus organisms for cell cycle

Answer 4

yeasts, frog eggs and mammalian cells in culture

Question 5

Hartwell

Answer 5

found first cdc genes and discovered checkpoints

Question 6

Hunt

Answer 6

discovered cyclin

Question 7

Nurse

Answer 7

Proved that MPF was cyclnin + CDK

and he isolated human cdk

Question 8

3 stages of CD cycle

Answer 8

Mitosis, synthesis and growth

Question 9

checkpoints

Answer 9

Points in the cell cycle where you can ‘put the breaks on’ due to cues/ have to pass ‘tests’
Regulated by cyclin/CDK complexes

Question 10

Examples of checkpoints

Answer 10

DNA damage, unfavourable extracellular environment (G1)
Incomplete repl (S)
Insufficient cell cycle (G2)
Chromosome incorrectly attache dto mitotic spindle (M)

Question 11

Cyclin/CDK complexes

Answer 11

allow 2 main checkpoints to be passed (from G2 into mitosis and G1 into S phase)

Question 12

CDK-cyclin complex formation

Answer 12

cdks constant throughout cell cycle
G2–> M: To make active complex they need to associate with cyclin proteins, which are synthesised during G2 and degraded at end of mitosis (m cyclin), or in the case of the G1–> S checkpoint the cyclin is synthesised during the G1 phase and degraded at the end of S phase (S-cyclin)

Question 13

When is peak in cdk activity and why (G2–>M)

Answer 13

Mid mitosis

Due to steady accumulation of M cyclin during G2 and then rapid destruction at the end of mitosis

Question 14

How is the peak in activity achieved? step 1

Why don’t we get a sharp incr

Answer 14

during cylin accumulation, the activity of the complex kept in check by phosphorylation of cdk (as complex is forming) by inhibitory kinase called Wee1- keeps cdk inactive

This is why we don’t get gradual increase in M-cdk (instead sharp)- see prev graph (green part)

Question 15

step 2

Forming active M-cdk

Answer 15

Once complex accumulated, activating phosphatase called Cdc25 removes phosphates from cdk
Forms active M-cdk complex

Question 16

step 3

+ve feedback

Answer 16

Active M-cdk/cyclin phosphorylates inactive Cdc25 (has no phosphatase activity), so it becomes active and can carry out phosphorylation
POSITIVE FEEDBACK

Question 17

Step 4

Drop in cdk activity

Answer 17

Drop in cyclin-cdk activity is rapid

APC activated, adds chains of ubiquitin to cyclins- tagging them for rapid destruction at proteosomes
forms inactive cdk because cyclin degraded

Question 18

What promotes transition of G1 into S phase

Answer 18

active S-cdk complex

Question 19

How does a G1/S phase checkpoint prevent repl of damaged dna

Answer 19

Protein machinery recognises different forms of DNA damage- activates p53 protein

Question 20

In absence of dna damage

Answer 20

p53 kept at low levels in the nucleus, being degraded (and a little synthesised ) by proteosomes

Question 21

If there is dna damage

Answer 21

Proteins phosphorylate p53, stop it being degraded (only synthesised) and activate it
p53 binds to target genes incl key gene p21 - cdk inhibitory protein(CIP). This protein (made from p21 gene) recognises and binds to cdk-complex, inactivates it so it can’t phosphorylate its target genes
ie p21 is a brake the cell can put on if there is dna damage

Question 22

p53 is a

Answer 22

TF (regulating p21) and tumour supressor (when p53 gene is mutated often results in cancers)

Question 23

cell cycle withdrawal

Answer 23

cells can exit the cell cycle and go into a G0 state- resting
Some stay there and never proliferate again, others wait to receive cues to go back into cell cycle

Question 24

Average rate of cell division varies based on

Answer 24

cell type

Question 25

Quiescent cells

Answer 25

Have withdrawn into G0 but have the capacity to re-enter the cell cycle (proliferation), cued by right signals
This involves regulation of the G1/S phase checkpoint by the retinoblastoma (Rb) protein

Question 26

G1

Answer 26

cell contents, excluding chromosomes are duplicated

Question 27

S

Answer 27

46 chromosomes duplicated

Question 28

G2

Answer 28

cell double check the dupl chromosomes for error making any needed repairs

Question 29

Control of cell proliferation by Rb

Answer 29

Holds onto TFs that activates genes that are involved in G1 to S transition
Various local signals can regulate this cell cycle control

Signal comes in and triggers intracellular signalling pathway
Results in accumulation of activated G1/S-Cdk, which (in S phase) phosphorylates Rb- changes conform (to become inactive) to release TFs which bind to genes required to initiate process of cell proliferation

Question 30

Mitogen signals

Answer 30

Promote cyclin synthesis and KIP/CIP degradation

Question 31

Terminal differentiatied cells

Answer 31

can be considered to be in a specific form of G0 state
Permanent withdrawal from the cell cycle
different to quiescent cells

Question 32

examples of terminally differentiated cells

Answer 32

neurones
keratinocytes in skin
Goblet (secretory) and enterocytes (absorptive)
Gut epithelial cells

Question 33

Senescence

Answer 33

for a normal cell, limit to number of times cell can divide (stem cells exception cancer cells evade senescence and are immortalised/transformed)

Question 34

Hayflick’s limit

Answer 34

human embryonic fibroblasts can only divide a finite number of times in culture

Question 35

When normal cells lose the capacity to divide, what post-mitotic state do they enter

Answer 35

Cellular or replicative senescence

in body or culture

Question 36

Contributing factors to senescence

Answer 36

Accumulation of KIPs/CIPs with more divisions- makes it harder to make enough active cyclin-cdk to go back into cell cycle
shortening of telomeres

Question 37

telomeres

Answer 37

WR

Question 38

cell number is a balance between

Answer 38

proliferation and apoptosis