Lecture 19: Cell cycle Flashcards
What two processes must be aligned for cell division to occur?
Chromosome division and cell division
What is the structure of the embryonic cell cycle?
S and straight to M
What is the structure of the somatic cell cycle?
Alternating S and M phases
Separated by gap phases
What are the two steps needed for cell division to occur?
Nuclear division
Cytoplasm division
What needs to happen for a cell to enter mitosis?
All DNA is replicated
All DNA is damage repaired
What needs to happen for a cell to enter S phase?
Growth stimulatory signals are present
Anti-proliferative signals are absent
Sufficient nutrients
What drives the cell cycle engine?
Cdk-Cyclin complex
What cyclin and cdk is involved in G1?
Cyclin D
Cdk 4 and 6
What cyclin and cdk is involved in G1/S?
Cyclin E
Cdk 2
What cyclin and cdk is involved in S?
Cyclin A
Cdk 2
What cyclin and cdk is involved in M?
Cyclin B
Cdk 1
Do cdk levels stay constant or change during the cell cycle?
Constant
Do cyclin levels stay constant or change during the cell cycle?
Rise and fall
How is cdk activated?
- Cyclin binds to Cdk
- Conformational change pulls T loop away from Cdk active site
- Substrate can bind
What are the four different ways of regulating cyclin-cdk complexes?
Phosphorylation
Ubiquitin-mediated proteolysis
Binding of CKI
Localisation
What is the effect of phosphorylation regulation?
Can be inhibitory or activating
What is the effect of regulation by ubiquitin mediated proteolysis?
Breaks down cyclin
Provides directionality
What is the effect of regulation by binding of CKI?
Cdk inhibitors are unregulated due to damage
What is the effect of regulation by localisation?
Cyclin B is imported to nucleus before mitotic
What is the function of checkpoints?
Ensure cell cycle and chromosome cycle are coupled
What is the overall process of getting in and out of mitosis?
- Switch off DNA damage checkpoints
- Activate Cdk1 to get into mitosis
- Silence spindle assembly checkpoint
- Inactivate Cdk1 to get out of mitosis
What is the process of step 1 getting into mitosis?
- Signalling pathways block Cdk1 activation
- Override G2/M checkpoint
What is the process of step 2 getting into mitosis?
- Cdk1 activation
- Phosphorylation of target proteins including other kinases
- Activates mitotic pathways and inactivates interphase pathways
- Brings about the morphological changes associated with mitosis
What is the process of step 3 turning off mitosis?
- APC is active in mitosis
- When all kinetochores attached SAC is silenced and APC is activatd
- Cyclin B is degraded
- Mitotic exit
- Securin degraded by APC
- Sister chromatid separation
What is the full overall process of turning mitosis off and on?
- DNA damage activates Wee1 to put inhibitory phosphates on Cdk1
- Cdc25 removes inhibitory phosphates leading to Cdk1 activation
- When all kinetochores are attached to spindle the APC is activated
- Cyclin B is ubiquitinated and degraded and Cdk1 is inactivated