Cell Cycle I

Question 1

What are the 3 major checkpoints

Answer 1

G1/s restriction point

G2/m

Sac- spindle assembly checkpoint (Metaphase)

Question 2

How does cdk affect cell cycle

Answer 2

Phosphorylates proteins when in complex with cyclin eg for chromosome condensation to progress cell cycle

Question 3

Cdk levels are constant, so how are they controlled

Answer 3

Changes in amount of cyclins eg via degradation through apc

Also regulated by phos/dephos by wee or cdc25

Question 4

Name the cdk and their cyclins in each stage

Answer 4

G1- cyclin D cdk 4/6

G1/s - cyclin E cdk 2

S - cyclin A cdk 2 or 1

G2/m - cyclin B cdk 1

Question 5

What is needed to activate cdk in cyclin complex

Answer 5

CAK (cdk activating kinase) at thr 160

Phosphorylates to activate

Question 6

What is cdk7 CAK in a trimer with

Answer 6

Cyclin H and mat1

Question 7

What inhibitory phos does wee1 or myt1 do

Answer 7

Wee1 and myt 1 via tyr 15

Myt1 also via thr 14

Question 8

What does cks1 do

Answer 8

Enhance affinity for cdk substrates via further phos

Also allows cyclin a and b apc degradation

Question 9

Which cdk inhibitors block cyclin D cdk4/6

Answer 9

P15,16,18,19 inks and p21

Question 10

Which 3 cdk inhibitors are important in blocking cyclin e/cdk2 in the g1/s restriction point

Answer 10

P21,27,57

Question 11

What removes the inhibitory phos of cdks via wee1 or myt1 eg on cdk1 m

Answer 11

Cdc25 a,b or c

Question 12

What’s the diff between cdc25 a b or c

Answer 12

A is for g1/s and g2/ m transition

B and c is in g2/m transition for cdk1

Question 13

When does cyclin b not activate cdk 1

Answer 13

If wee1 present

Question 14

Explain ubiquitin proteasome degradation in end of mitosis or g1/s

Answer 14

E1 undergoes atp hydrolysis to gain a ub

Transfers to e2

E3 ligase then attaches and causes poly ubiquitination

Poly ub chains on the protein eg cyclin B allows proteasome degradation

Question 15

What are 2 examples of e3 ub ligase

Answer 15

Scf and apc

Question 16

What is scf present for

Answer 16

G1/s transition eg cyclin e degradation

Question 17

What allows scf degradation

Answer 17

Only when proteins like cyclin e become phosphorylated can it recognise it via f box

Question 18

Which part of scf adds ub chains in g1/s

Answer 18

F box proteins

Question 19

What is apc

Answer 19

An e3 ligase

Anaphase promoting complex

Works through m phase

Question 20

What is the ring finger domain of apc called

Answer 20

Apc11

Question 21

What does apc degrade in m phase

Answer 21

Securin, cyclin a and b (helped by cks1)

Question 22

What coactivators are needed with apc

Answer 22

Cdc20 or cdh1

Question 23

What does cdk oscillator mean

Answer 23

Cdk can cause it’s own inactivation via activating apc cdc20 at start of mitosis phase

This causes cyclin b deg causing its own inactivation

Apc cdc20 then also inactivated so cyclin b rises when cdk is low

Question 24

What stops cyclin b rising too high after apc cdc20 inactivation

Answer 24

Apc cdh1- through end of m phase and into g1/ s keeps cyclin b low so it can undergo another cell cycle

Question 25

Without inactivation via p16,21,27,57 what occurs in restriction point

Answer 25

Cyclin d/4/6 and cyclin e /2 and cyclin a/cdk1/2 can cause phos of Rb p107 protein

This release e2f which causes expression of s phase proteins like dna pol and cyclin e/a = s phase transition

Question 26

What would reverse inhibition of restriction point by p16 etc

Answer 26

Mitogens or gf which signal repair etc

Question 27

What does dna damage activate

Answer 27

Atm or atr which phosphorylate chk1 or 2

Question 28

What does chk1 phos cause from atm/atr damage response

Answer 28

Chk1 will phosphorylate and inactivate cdc25a

This means cdk1 is not activated as wee1 is constant in action but cdc isnt

This causes arrest and block of m phase

Either repaired or apoptosis occurs

Question 29

What does phos of chk2 do

Answer 29

Causes activation of p53

P53 then acts on p21 genes and stabilises p21

P21 blocks both cyclin d and e cdk so no g1/s transition as e2f isn’t released from rb

Question 30

What type of complex forms on origin in g1 to start rep in s

Answer 30

Pre replicative complexes

Question 31

What in s phase allows helicase activity

Answer 31

Ddk

Question 32

How does s- cdk stop re rep

Answer 32

Prevents cdc6 and mcm binding to orc

Question 33

What is the pre rep complex

Answer 33

Orc origin recognition complex binds cdt1 and cdc6 to then allow mcm helicase binding

Question 34

What protein binds cdt1 till it is degraded by apc in m phase to prevent re rep

Answer 34

Geminin

Question 35

What complex forms primers for replication

Answer 35

Pol a primase

Question 36

Which polymerases pick up from pol a primers

Answer 36

Pol d or e

Question 37

Which proteins bind to stop annealing of unwound dna from origin

Answer 37

Rpa

Rep protein a

Question 38

What adds motifs on the lagging 3’ strand which is hard to replicate

Answer 38

Telomerase to stop chromosome shortening

Question 39

What needs to assemble during s phase

Answer 39

Chromatin nucleosomes

Question 40

How is an octamer assembled in s phase

Answer 40

The h3,4 tetramer is assembled via CAF1

Then h2ab dimer x2 is assembled on it via NAP1

Reattached to rep fork and incorporated into dna

Question 41

Which methylations on n terminal tail are for heterochromatin

Answer 41

H3 k9 and k27

Question 42

Which phos mods of histone n terminal tails happen for mitosis

Answer 42

H3 thr 3

H3 ser 10

Question 43

Which phosphorylation is correlated to dna damage

Answer 43

H2ax ser139

Question 44

What removes HP1 from H3 k9 via H3 ser 10 phos

Answer 44

Aurora B

Question 45

What is this called

Answer 45

Phosphomethyl switch