Lecture 19 - control of the cell cycle Flashcards
what cell phases do embryonic cells have
S and M
(oscillators)
so just move from one to the other
what are the 2 steps in M phase
- nuclear division - mitosis
- division of cytoplasm - cytokinesis
what occurs in S phase
Dna replication
what happens at end of G phase
- checks if environment favourable
Are growth stimulatory signals present?
Are anti-proliferative signals absent?
Are there sufficient nutrients?
Is there any “damage” - if damage then ye cuz it needs to multiply
what complex drive the cell cycle engine
Cdk-cyclin complexes
(cyclin dependent kinase)
What are the Cdk that bind to cyclin D, E, A and B
Cdk4 and cdk6
Cdk2
Cdk2
Cdk1
What phases do cyclin D E A and B appear in respectively
G1
G1/s
S
M
what occludes the active site of Cdk, making it inactive
T-loop
how does cyclin activate the Cdk
conformational change
pulls the t loop away
substrates can now bind
what 4 things can regulate the cyclin-Cdk complexes
- inhibitory/activating phosphorylations of the cdk
- ubiquitination
- CKI (cyclin dependent kinase inhibitor)
- localisation of the cyclins
where are the key checkpoints in the cell phases
end of G1
end of G2
during mitosis before the cells are split
what needs to be activated to allow mitotic phase to start
Cyclin B - cdk1 complex
what protein adds 2 inhibitory phosphates onto CycBCdk1
Wee1
what protein dephosphorylates CycBCdk1 to activate it again
Cdc25
what happens when a little bit of CycBCdk1 is made
pushes a +ve feedback loop
more cdc25 activated
wee1 inhibited
so overall more CycBCdk1 is made
what things does CycBCdk1 do in the cell to bring about mitosis
- chrom condensation
- breakdown of nuclear envelope
- spindle assembly by making microtubules more dynamic
what happens at the G2/M checkpoint
ensure no damaged DNA left before moving to mitosis
what happens if there is damaged DNA at G2/M checkpoint
repair pathwayz are triggered
which will fix the dna obviously
but also inhibit cdc25 and activate wee1
so no CycBCdk1 is made
and mitosis doesnt start
how do we get out of mitosis
inactivation of CycBCdk1
via ubiquination of the cyclin B part
which marks it for proteolysis
cycB destroyed and poor Cdk is on its own again
what is the thing that ubiquinates the cyclin B
APC
anaphase promoting complex (aka E3 ubiq ligase)
what will block APC from becoming active
spindle assemble checkpoint (SAC)
which is kept active by unattached kinetochores
what else other than cyclin B is degraded by APC
securin
so sister chromatids can separate
and anaphase happens
