Cell Cycle I Flashcards
What are the 3 major checkpoints
G1/s restriction point
G2/m
Sac- spindle assembly checkpoint (Metaphase)
How does cdk affect cell cycle
Phosphorylates proteins when in complex with cyclin eg for chromosome condensation to progress cell cycle
Cdk levels are constant, so how are they controlled
Changes in amount of cyclins eg via degradation through apc
Also regulated by phos/dephos by wee or cdc25
Name the cdk and their cyclins in each stage
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
What is needed to activate cdk in cyclin complex
CAK (cdk activating kinase) at thr 160
Phosphorylates to activate
What is cdk7 CAK in a trimer with
Cyclin H and mat1
What inhibitory phos does wee1 or myt1 do
Wee1 and myt 1 via tyr 15
Myt1 also via thr 14
What does cks1 do
Enhance affinity for cdk substrates via further phos
Also allows cyclin a and b apc degradation
Which cdk inhibitors block cyclin D cdk4/6
P15,16,18,19 inks and p21
Which 3 cdk inhibitors are important in blocking cyclin e/cdk2 in the g1/s restriction point
P21,27,57
What removes the inhibitory phos of cdks via wee1 or myt1 eg on cdk1 m
Cdc25 a,b or c
What’s the diff between cdc25 a b or c
A is for g1/s and g2/ m transition
B and c is in g2/m transition for cdk1
When does cyclin b not activate cdk 1
If wee1 present
Explain ubiquitin proteasome degradation in end of mitosis or g1/s
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
What are 2 examples of e3 ub ligase
Scf and apc
What is scf present for
G1/s transition eg cyclin e degradation
What allows scf degradation
Only when proteins like cyclin e become phosphorylated can it recognise it via f box
Which part of scf adds ub chains in g1/s
F box proteins
What is apc
An e3 ligase
Anaphase promoting complex
Works through m phase
What is the ring finger domain of apc called
Apc11
What does apc degrade in m phase
Securin, cyclin a and b (helped by cks1)
What coactivators are needed with apc
Cdc20 or cdh1
What does cdk oscillator mean
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
What stops cyclin b rising too high after apc cdc20 inactivation
Apc cdh1- through end of m phase and into g1/ s keeps cyclin b low so it can undergo another cell cycle
Without inactivation via p16,21,27,57 what occurs in restriction point
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
What would reverse inhibition of restriction point by p16 etc
Mitogens or gf which signal repair etc
What does dna damage activate
Atm or atr which phosphorylate chk1 or 2
What does chk1 phos cause from atm/atr damage response
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
What does phos of chk2 do
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
What type of complex forms on origin in g1 to start rep in s
Pre replicative complexes
What in s phase allows helicase activity
Ddk
How does s- cdk stop re rep
Prevents cdc6 and mcm binding to orc
What is the pre rep complex
Orc origin recognition complex binds cdt1 and cdc6 to then allow mcm helicase binding
What protein binds cdt1 till it is degraded by apc in m phase to prevent re rep
Geminin
What complex forms primers for replication
Pol a primase
Which polymerases pick up from pol a primers
Pol d or e
Which proteins bind to stop annealing of unwound dna from origin
Rpa
Rep protein a
What adds motifs on the lagging 3’ strand which is hard to replicate
Telomerase to stop chromosome shortening
What needs to assemble during s phase
Chromatin nucleosomes
How is an octamer assembled in s phase
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
Which methylations on n terminal tail are for heterochromatin
H3 k9 and k27
Which phos mods of histone n terminal tails happen for mitosis
H3 thr 3
H3 ser 10
Which phosphorylation is correlated to dna damage
H2ax ser139
What removes HP1 from H3 k9 via H3 ser 10 phos
Aurora B
What is this called
Phosphomethyl switch
