Cell cycle control Flashcards
What are the stages in the Cell cycle?
• Stages: Gap1, Synthesis (DNA), Gap2, Mitosis.
What happens if the cycle isn’t regulated?
• Cycle is regulated – if this fails cancer (if DNA is being repaired then shouldn’t got to M).
What is vital to control progression through checkpoints?
• Cyclin level variation during the cell cycle is vital to control progression through checkpoints:.
What are the checkpoints? How many are there?
o G1S
o G2M
o MA.
What have Cell fusion & cytoplasm injection experiments showed? What phase is activated in nucleus and what is activated in original non-M nucleus?
o Material from older cells make younger cells jump ahead even if they aren’t ready.
o S+G1 = S phase is activated in original G1 nucleus.
o M+G1 = M phase is activated in original non-M nucleus.
• Therefore, signals must be sent.
What signals are needed at check points?
- Stop and go signals: internal & external signals at the checkpoints:
• Animals have built in stop signals that stop cycle until overridden by go signals.
• Many go signals are from cellular surveillance mechanisms inside the cell which tell if the crucial processes have been carried out and thus whether the cycle should proceed or not.
• Checkpoints also register signals from outside the cell e.g. growth factors release by cells promoting division cause other cells to divide.
Outline the importance of each checkpoint.
• 3 main checkpoints:
o G1- restriction point – most important – if passes this checkpoint usually whole cycle will be completed. If go ahead not received then it may exit cycle into G0 (nondividing state)
o G2 -
o M – will not pass if a stop signal shows any chromosomes not attached to spindle. Only when kinetochores of all chromosomes are properly attached will the go ahead be given.
What is MPF? What is it made from? What do these components do?
- Mitotic promoting factor cdk+cyclin
- MPF is a kinase enzyme that switches on/off the target cell cycle protein by phosphorylating
- MPF promoted entrance to mitosis from G2 by phosph proteins during mitosis that leads to destruction of cyclin
- Cdk= cell division control protein (cyclin dep kinase) active when bound to cyclin
- Cyclin= protein whose amount vaies cyclically. When in high concentrations binds to cdk and make MPF and favours mitosis.
What is a cyclin?
• Cyclins: proteins that vary in level through the cell cycle & bind to Cdks to activate them = POSITIVE signal. Increases during cell cycle.
What is a cdk?
• Cdk: cyclin dependant kinases – activated by binding to cyclins although this doesn’t guarantee full activity. Further activation depends on phosphorylation.
What is a CAK?
• CAK: Cdk activating kinase.
Sketch how mitotic cdk-cyclin complex becomes active from its constituents.
pic in notes.
Describe Regulation of Cdk-Cyclin by phosphorylation & dephosphorylation:.
- Activation of mitotic Cdk-Cyclin involves addition of inhibiting & activating phosphate groups
- Addition of two inhibiting phosphates by tyrosine kinase (wee1)
- Addition of activation phosphate.
- Followed by removal of the inhibiting phosphate groups by a phosphatase(Cdc25).
- Once removal of inhibiting groups, followed by removal of the positive feedback loop is set up: the activated Cdk-Cyclin (MPF) complex generated by this reaction stimulates the phosphatase.
- This causes the activation process to proceed more rapidly.
Once active what does the Cdk-cyclin complex do?
• Once active the complex stimulates: o Nuclear envelope(lamina) breakdown- phosphorylation of lamina. o Chromosome condensation. o Mitotic spindle formation. o Targeted protein degradation.
Sketch the mitotic spindle checkpoint.
notes.
