Control of the cell cycle
- Created by: Alice Fisher
- Created on: 07-05-15 13:26
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- 9 Control of the cell cycle
- Checkpoints
- Cells grow between stages of division so there is enough cytoplasm for cell division
- 1)G1 phase; nutritional and environmental checking. Stage maintains cell size
- 2)Restriction point; what cells have to pass through to enter the S phase. In yeast this is the start
- S phase; DNA replication. Check if environment is favourable.
- G2; more growth, more cell checks
- At the end of each stage the cells are checked for errors
- Mitosis; check environment favourable and if DNA replicated. Anaphase; check if chromosomes are properly attached to spindle
- Work though negative signalling. The difference in positive signal intensity between 45 and 46 chromosomes would be hard to differentiate leading to fatal errors
- Any unattached chromosomes therefore send negative signals that inhibit the cycle. As soon as all are attached, a positive signal is sent
- Unattached chromosomes leads to inhibition of the anaphase promoting complex and anaphase arrest (APC activates the UPS)
- Inhibition of cyclin degradation (if APC is inactivated) results in anaphase arrest
- Unattached chromosomes leads to inhibition of the anaphase promoting complex and anaphase arrest (APC activates the UPS)
- Nature of the signals are phosphorylations and proteolysis
- Any unattached chromosomes therefore send negative signals that inhibit the cycle. As soon as all are attached, a positive signal is sent
- Detection of S phase
- Fluorescent dna dyes used to determine DNA content in a flow cytometer or fluorescence-activated sorter (FAC's)
- 3H-thymidine incorporation revealed by autoradiography
- Bromo-deoxyuridine (BrdU) incorporation visualised by anti-BrdU antibodies
- Mitosis
- 1)Prophase; chromosomes visible 2)Prometaphase; chromosomes move to cell centre 3)Metaphase;chromosomes attach to microtubules in cell centre
- 4)Anaphase; chromosomes pull apart 5)Telophase; spindle detaches 6)Cytokinesis; cytoplasm divides
- Takes about an hour in humans. Interphase can last 16 hours to a lifetime
- In frogs eggs cell growth happens without dividing and then divides rapidly
- Cdk's (cyclically dependent kinases)
- Requires cyclin for activation. CDk further regulated by phosphorylation/dephosphorylation. They are relatively small proteins (34 to 40KDa)
- Binds to a regulatory protein called a cyclin. Only cyclin-CDK is an active kinase
- CDK levels relatively constant. Cyclin is synthesised and degraded (by the ups) throughout cell cycle
- Mitotis cyclins accumulate during G2. Once at a high conc they can bind to cdk's. When multiple ones bind, the resulting complex is known as mitosis-promoting factor (MRF). Signal for G2 to enter mitosis.
- Mitosis positive feedback further activated in late G2 by phosphatases
- Mitotis cyclins accumulate during G2. Once at a high conc they can bind to cdk's. When multiple ones bind, the resulting complex is known as mitosis-promoting factor (MRF). Signal for G2 to enter mitosis.
- CDK levels relatively constant. Cyclin is synthesised and degraded (by the ups) throughout cell cycle
- Errors in cell cycle
- DNA Damage, lagging chromosomes (aneuploidy)
- Unchecked division can lead to cell death, hyperplasia, cancer
- Withdrawal from the cycle. Senescence (ceases to divide) and differentiation
- Checkpoints
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