Cell cycle in Eukaryotes Flashcards
What is the cell cycle
- Repeated process by which the cell duplicates itself and divides into two daughter cells
- Continuous cell divisions since beginnings of life on earth
- The cell cycle is controlled
- embryos show co-ordinated waves of cell division
What can the loss of cell cycle control result in
- Loss of cell cycle control is a key step in cancer formation
- Identifying regulators of the cell cycle is important:
- tumour suppressors or proto-oncogenes
- predict people at risk
- potential drug targets
What are the basic events in the cell cycle
- Duplicate cytoplasmic components (cell growth)
- Chromosome duplication
- Chromosome segregation
- Cytoplasmic segregation
What happens in Prophase
- The chromosomes begin to condense.
- The centrosomes begin to assemble at the poles of the cell.
- Nuclei starts to breakdown- no longer nuclear envelope
What happens in Prometaphase
- Microtubules from centrosomes start to project and radiate out into cells
What happens in Metaphase
- The chromosomes align along the plane that bisects the cell and become attached to the microtubule fibres of the mitotic spindle.
What happens in Anaphase
- Segregation occurs; the sister chromatids are pulled apart by the mitotic spindle to the two opposite poles of the cell.
What happens in telophase
- The chromatids de-condense and a new nuclear membrane forms around each new set of chromosomes.
How is the cell cycle regulated
- Controlled by checkpoints
- If problem- there is a pause for it to be rectified or for cell to exit cell cycle and not divide
- Checkpoints there to detect problem in External and Internal environment
What happens in the first checkpoint
- Check if favourable internal environment
- Right number of organelles
- Correct amount of duplication etc
What is checked at the second checkpoint
- All DNA needs to have been duplicated
What is checked at the third checkpoint
- Make sure anaphase is triggered at correct time
What may happen without the first checkpoint
- Start checkpoint
- Inappropriate cell proliferation
- lack of nutrients
- → cell death
- → malformed tissues
- → cancer
What may happen without the G2/M checkpoint
- Division without complete DNA duplication
- daughter cells lack full complement of chromosomes (aneuploidy)
- → cell death
- → cancer
What may happen without the Metaphase/Anaphase transition checkpoint
- Division with incomplete chromosome attachment
- daughter cells with uneven amounts of DNA (aneuploidy)
- → cell death
- → cancer
How is progression through the checkpoints controlled?
- Cyclins and cyclin-dependent kinases
- Cyclin-dependent kinases (cdk) phosphorylate target proteins
- Cyclins are regulatory proteins which bind cdks and allow them to become active
The level of what changes throughout the cell cycle
- Cdk levels do not change throughout the cell cycle.
- It is the levels of cyclins that go up or down; this in turn controls the activation status of cdks.
- Transcription levels of many other genes are also controlled during the cell cycle.
Describe levels of G1/S cyclins and complexes through progression of cell cycle
- G1/S-cyclins levels rise during late G1 Phase and form G1/S-Cdk complexes.
- The G1/S-Cdk complexes will reach high levels that that allow progression through the Start checkpoint.
- G1/S-cyclins levels they start off low in G1, rise and remain high until the end of M phase where they drop to low levels again.
Describe levels of S-cyclin and complexes through progression of cell cycle
- S-cyclin levels start to rise following progression through the Start checkpoint.
- S-Cdk complexes reach high levels at the start of S phase triggering downstream events.
- S-cyclin levels begin to drop following the G2/M checkpoint and reach basal levels at the metaphase-anaphase transition checkpoint.
Describe levels of m-cyclin and complexes through progression of cell cycle
- M-cyclin levels begin to rise in G2.
2. M-Cdk complexes are formed but remain inactivated until the end of G2.
What is APC/C
- APC/C initiates cell progression through the metaphase-anaphase transition checkpoint.
- Anaphase promoting complex
How are Cdk levels regulated
- Phosphorylation
- Binding of inhibitory proteins
- Proteolysis
- Localisation
- Feedback loops
- Transcription
How is cdk regulated by binding of inhibitory proteins
- Cdk regulation- binding of inhibitory proteins
- Bind to entire complex- cyclin-cdk complex
- Not active if bound
How is cdk regulated by phosphorylation
- reaction in which a phosphate group is covalently coupled to another molecule
- Cdk needs a kinase to add a phosphate group to allow it to activate
- Other regions on cdk other phosphate groups can be added which can be inhibitory and put it in inactive state even with binding of cyclin and activating phosphate
How is cdk regulated by proteolysis
- Degradation of protein by hydrolysis at one or more of its peptide bonds
- Ubiquitination- Ubiquitin tag proteins are transported to proteasomes where they are degraded
- Can then be recycled
- Ubiquitin ligase added ubiquitin onto cyclins
- Cyclin is targeted for degradation not cdk
- But if cyclin is degraded it cant bind to cyclin dependent partner- cdk
How is cdk regulated by localisation
- If proteins are in different local areas of cell can’t physically interact
- E.g. nucleus and cytoplasm
How is cdk regulated by feedback loops
- Feedback and feed-forward networks are responsible for many of the complex biological behaviours we see in signalling.
- Feedback is observed when the output from a given node follows a path of links that returns to regulate the node of origin.
- Distinct from negative and positive regulation – regulation is a result of the pathway activity
