Download Cell cycle and its regulation

Cell cycle and its regulation
Seminar of molecular and cell biology
Mgr. Jan Šrámek
[email protected]
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Syllabi
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Cell cycle (CC) phases
G0 phase and resting cells
Cell cycle cycles
Phases of mitosis and meiosis
Cytokinesis
Mechanisms of cell cycle and its regulation
Cell cycle checkpoints
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Revision
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Cell cycle phases
Cell cycle cycles
Phases of mitosis and meiosis
Cytokinesis
G0 phase and resting cells
Mechanisms of cell cycle regulation
Cell cycle checkpoints
Questions:
1. What is the sense of CC?
2. What are the cell cycle phases
3. What is the duration of CC and is it same for all types of cell?
4. What occurs during S phase of CC?
5. What occurs in G2 phase of CC?
6. How are cell organelles doubled?
7. Are there any morphological changes during cell division?
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Cell cycle phases
6h
12h
6h
1h
Blebs & microvilli
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Cell cycle phases
G1 phase
▫ doubling of cell content
▫ growth of cell
▫ production of proteins and RNA
▫ preparation for replication process
S phase
▫ replication process
G2 phase
▫ doubling of organelles and function capacities of cell
M phase
▫ mitosis and cytokinesis
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Revision
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Cell cycle phases
Cell cycle cycles
Phases of mitosis and meiosis
Cytokinesis
G0 phase and resting cells
Mechanisms of cell cycle regulation
Cell cycle checkpoints
Qeustions:
1. What are the CC cycles?
2. Are these cycles reciprocaly independent?
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Cell cycle cycles
Cell cycle includes following reciprocally coordinated processes:
▫ DNA synthesis
▫ nuclear division
▫ growth cycle
▫ cell division
▫ centrosome cycle
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Revision
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Cell cycle phases
Cell cycle cycles
Phases of mitosis and meiosis
Cytokinesis
G0 phase and resting cells
Mechanisms of cell cycle regulation
Cell cycle checkpoints
Qeustions:
1. What happens with choromosomes during mitosis?
2. Name all phases of mitosis?
3. What happens in repsective phases of mitosis?
4. Describe difference between mitosis and meiosis?
5. In which cells meiosis occur?
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Mitosis phases
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Revision
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Cell cycle phases
Cell cycle cycles
Phases of mitosis and meiosis
Cytokinesis
G0 phase and resting cells
Mechanisms of cell cycle regulation
Cell cycle checkpoints
Qeustions:
1. What happens with choromosomes during mitosis?
2. What are the phases of mitosis and what happens in respetive phases?
3. What is the difference between mitosis and meiosis?
4. In which cells meiosis occur?
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Mitosis vs. meiosis
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Mitosis vs. meiosis
Haploidní dceřiné buňky
Diploidní dceřiné buňky
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Mitotic spindle
Includes microtubular fibres (kinetochores, astral and overlap microtubules),
centrosomes, microtubule-associated proteins, motor proteins
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Kinetochore in prophase
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Growing + ends of polar microtubules are stabilizing (no retrograde shortening
according to dinamic instability)
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Molecular motors usage
Separation of centrosomes to oposite poles of the cell (anaphase) is processed according to
molecular motors (MM) movement along polar microtubules and according to MM activity on
cytoplasmic membrane of oposite poles of the cell.
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Kinetochore in anaphase
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Alternative forms of chromosome attachement
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Chromatids are under constant pressure generated by kinetochore
microtubule.
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Chromatids separation possibilities
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Revision
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Cell cycle phases
Cell cycle cycles
Phases of mitosis and meiosis
Cytokinesis
G0 phase and resting cells
Mechanisms of cell cycle regulation
Cell cycle checkpoints
Questions:
1. Which specific cell structures participate in cytokinesis process?
2. Is cytokinesis processed in each types of cell identicaly?
3. Can CC be finished without cytokinesis?
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Cytokinesis
• Starts durring mitotic anaphase after nuclear division and cellular
components doubling.
• Leads to approximately equal division of cellular components (cytoplasm,
organelles). In some cases asymetric division (embryonal cells)
• New cellular boundary is formed at the equator of the mitotic spindle.
• Differences among different cell types (animals, plants, yeasts).
• Involves contractile ring formation in animal cells (actin-myosin structure).
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Actin – red
Myosin - green
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Regulation of contractile ring formation
MPF – mitose promoting factor, dimer
of Cdc2 and cyklin B
MPF  phosphorylation of myosin
filaments  inhibition of association
with actin
MPF degradation  dephosphorylation
of myosin filaments  activation
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Regulation of contractile ring
formation
RhoA subsequently leads to actin-myosin
contraction via formin and Rho-activated kinases
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Plant cells division includes cell wall development
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Binar division
in Bacteria
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Endoreduplication
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Replication of the nuclear genome in the absence of cell and nuclear division
Leads to elevated nuclear gene content and polyploidy
Specific cell cycle variant: G1  S  G2  G1
Widespread in plants, rarely in animal cells, common phemonema in cancer cells
Endocycle vs. endomitosis
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Revision
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Cell cycle phases
Cell cycle cycles
Phases of mitosis and meiosis
Cytokinesis
G0 phase and resting cells
Mechanisms of cell cycle regulation
Cell cycle checkpoints
Questions:
1. Is G0 phase part of the CC?
2. Which types of G0 cells we know?
3. From which phase of CC can cell enter into G0 phase?
4. What are the basic characteristics of resting cells?
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G0 phase
Stem cells vs. cells in terminal stadium of differentiation
Entering to G0 phase from G1 (rarely from G2 phase)
After G0 phase back to G1 phase
Resting cells characteris:
▫ Constant size
▫ Protein and RNA synthesis regulation
▫ Generally lower metabolic activity
▫ More resistant to stresses
▫ Myc, CDKs and Cyklins protein level
decrease
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Revision
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Cell cycle phases
Cell cycle cycles
Phases of mitosis and meiosis
Cytokinesis
G0 phase and resting cells
Mechanisms of cell cycle regulation
Cell cycle checkpoints
Questions:
1. Define terms activation and progression of CC.
2. Explain terms genes of primary and secondary response?
3. Which proteins/protein complexes are involved in cell cycle regulation?
4. What are the main proteins responsible for CC activation?
5. Are there some inhibitors of CC?
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Mechanisms of cell cycle regulation
Activation (G0  G1) x progression (G1  S  G2  M)
Genes of primary and secondary response
Basic role of various cyclins, Cdks, substrates and Cdk inhibitors
Many other proteins (or comlexes) are involved (MPF, APC/C, Cdc25, Wee1
….)
Regulators of cell cycle:
1. Cyklins – catalytic subunits of cyclin-cdk complexes, their protein level is
oscilating
2. Cdks – their activity is regulated via cyclin binding, phosphorylations and
dephosphorylations and via Cdk inhibitors
3. Substrates of cyclin-cdk complexes – Rb family proteins
4. Cdk inhibitors – bind and inactivate Cdks; INK4 and p21 family
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Cell cycle entry and S phase initiation via Rb protein
G0  G1
G1  S
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Cell cycle entry and S phase initiation via Rb protein
G0  G1
G1  S
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Cdk activation
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Different cyclins and Cdks are involved in different stages of cell cycle progression
and regulation
Cyclin E + Cdk2
Cyklin B + Cdk1 (Cdc2)
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APC/C role in chromatid separation
APC – anaphase promoting complex
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The control of proteolysis by APC/C
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APC/C role in cell cycle regulation
MPF – dimer of Cdc2 and cyklin B
= mitose promoting factor
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APC/C role in cell cycle regulation
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CKI (p27) role in cell cycle regulation
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The control of CKI aktivity by SCF
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Cell cycle checkpoints
Anables to stop or slow down cell cycle via specific signaling pathway (comprising p21
inhibitors) according to DNA damage, disturbed replication process or mitotic
chromosomes misfold.
Restriction point – regulation point in G1 phase, when passed cell is determined to
continue cell cycle independently of mitogenes, similar to yeast’s
START point
DNA replication checkpoint – in G2 phase, cotrole of appropriate DNA replication
Spindle assembly checkpoint – controle of appropriate chromosome segragation
during mitosis, in M phase
DNA damage checkpoint – controle of DNA damage, in G1, S (PCNA) and G2 phase
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Cell cycle checkpoints
4.
3.
2.
1.
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Cell cycle arrest
- via inhibition of Cdk using p53
PCNA
Inhibition of DNA
replication
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p53 activation
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Diseases connected with cell cycle regulation disordes
Cancer – many types, crucial role of regulator proteins p53, p21, p27, Rb
Cardiovascular diseases – cyclin-CDK-CKI interactions disorder (atheriosclerosis)
CNS diseases
Renal diseases – crucial role of CKI (p27)
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Rb protein role in cancer development
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Role of p53 (p21 or p27)
in cancer development
PCNA
Inhibition of DNA
replication
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Thanks for attention…