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CELL CYCLE
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SIGNIFICANCE OF THE CELL CYCLE
IN MEDICINE
Example:
• Cell cycle: nondisjunction → trisomy
• Disorder: trisomy 13 (Patau syndrome)
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CELL CYCLE:
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Function of the cell cycle
Phases of the cell cycle
Functional periods of the cell cycle
DNA replication
Nuclear division (mitosis)
Cell division (cytokinesis)
Doubling of functional capacities of the cell
Resting cells
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1. FUNCTION OF THE CELL CYCLE:
Cell reproduction is accomplished within the framework of the cell cycle:
parental cell → 2 daughter cells
Division resulting in more or less equal daughter cells requires:
• Precise doubling of the genetic material
• Doubling of other functional capacities of the cell
Duration of the cell cycle: variable (significantly shortened cell cycle
of early embryonic cells) [FIG.]
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2. PHASES OF THE CELL CYCLE:
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Nuclear division (mitosis) & cell division (cytokinesis)
Interphase
Phases of the cell cycle:
• G1 phase (G derived from „gap“)
• S phase (S derived from „synthesis“): DNA replication
• G2 phase
• M phase (M derived from „mitosis“): mitosis & cytokinesis
[FIG.]
Phase specific changes of morphology and physiology of the cell: blebs &
microvilli, rounding when entering mitosis, RNA synthesis and protein synthesis
Duration of cell cycle phases
[FIG.]
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2. PHASES OF THE CELL CYCLE:
•
•
Nuclear division (mitosis) & cell division (cytokinesis)
Interphase
Phases of the cell cycle:
• G1 phase (G derived from „gap“)
• S phase (S derived from „synthesis“): DNA replication
• G2 phase
• M phase (M derived from „mitosis“): mitosis & cytokinesis
[FIG.]
Phase specific changes of morphology and physiology of the cell: blebs &
microvilli, rounding when entering mitosis, RNA synthesis and protein synthesis
Duration of cell cycle phases
[FIG.]
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3. FUNCTIONAL PERIODS OF THE CELL
CYCLE:
Basic functional periods of the cell cycle:
• DNA replication: S phase
• nuclear division (mitosis): M phase
• cell division (cytokinesis): M phase
• doubling of functional capacities of the cell: G1 → G2
Cell cycle involves several functional cycles:
• DNA synthesis cycle
• nuclear division cycle
• growth cycle
• cell division cycle
Independent function of the cycles: egg cleavage, meiosis, endoreduplication
[FIG.]
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4. DNA REPLICATION:
DNA replication: DNA duplication, semiconservative character (template and
complementary strand) [FIG.]
Organization of DNA replication: replication unit (replicon), replication origin,
replication fork
Mechanism of DNA replication:
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DNA polymerase: DNA replication itself
Helicase: unwinding of double-stranded DNA
Primase: primer
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leading strand: new strand in 5´ → 3´ direction (DNA polymerase δ)
lagging strand: new strand in 3 ´→ 5´ direction (DNA polymerase α), Okazaki
fragments,
DNA ligase [FIG.] [FIG.]
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Joint synthesis of histones
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4. DNA REPLICATION:
DNA replication: DNA duplication, semiconservative character (template and
complementary strand) [FIG.]
Organization of DNA replication: replication unit (replicon), replication origin,
replication fork
Mechanism of DNA replication:
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•
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DNA polymerase: DNA replication itself
Helicase: unwinding of double-stranded DNA
Primase: primer
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•
leading strand: new strand in 5´ → 3´ direction (DNA polymerase δ)
lagging strand: new strand in 3 ´→ 5´ direction (DNA polymerase α), Okazaki
fragments,
DNA ligase [FIG.] [FIG.]
•
Joint synthesis of histones
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4. DNA REPLICATION:
DNA replication: DNA duplication, semiconservative character (template and
complementary strand) [FIG.]
Organization of DNA replication: replication unit (replicon), replication origin,
replication fork
Mechanism of DNA replication:
•
•
•
DNA polymerase: DNA replication itself
Helicase: unwinding of double-stranded DNA
Primase: primer
•
•
leading strand: new strand in 5´ → 3´ direction (DNA polymerase δ)
lagging strand: new strand in 3 ´→ 5´ direction (DNA polymerase α), Okazaki
fragments,
DNA ligase [FIG.] [FIG.]
•
Joint synthesis of histones
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5. NUCLEAR DIVISION (MITOSIS):
Mitosis and cytokinesis are mostly joint processes.
Chromosome condensation: 10 000x
Centrosome cycle: centrosome (centrioles) [FIG.]
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Mitotic phases:
• Prophase: chromosome condensation (two sister chromatids) [FIG.]
[FIG.]
• Prometaphase: disintegration of nuclear envelope (nuclear lamina:
lamins), microtubules of mitotic spindle attached to chromosomes
(kinetochore) [FIG.] [FIG.]
• Metaphase: chromosomes in equatorial position
• Anaphase: separation of sister chromatids → loosened chromatids
go towards the poles of mitotic spindle [FIG.] [FIG.]
• Telophase: reintegration of nuclear envelopes
[FIG.] [FIG.]
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Mitotic phases:
• Prophase: chromosome condensation (two sister chromatids) [FIG.]
[FIG.]
• Prometaphase: disintegration of nuclear envelope (nuclear lamina:
lamins), microtubules of mitotic spindle attached to chromosomes
(kinetochore) [FIG.] [FIG.]
• Metaphase: chromosomes in equatorial position
• Anaphase: separation of sister chromatids → loosened chromatids
go towards the poles of mitotic spindle [FIG.] [FIG.]
• Telophase: reintegration of nuclear envelopes
[FIG.] [FIG.]
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Mitotic phases:
• Prophase: chromosome condensation (two sister chromatids) [FIG.]
[FIG.]
• Prometaphase: disintegration of nuclear envelope (nuclear lamina:
lamins), microtubules of mitotic spindle attached to chromosomes
(kinetochore) [FIG.] [FIG.]
• Metaphase: chromosomes in equatorial position
• Anaphase: separation of sister chromatids → loosened chromatids
go towards the poles of mitotic spindle [FIG.] [FIG.]
• Telophase: reintegration of nuclear envelopes
[FIG.] [FIG.]
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Mitotic phases:
• Prophase: chromosome condensation (two sister chromatids) [FIG.]
[FIG.]
• Prometaphase: disintegration of nuclear envelope (nuclear lamina:
lamins), microtubules of mitotic spindle attached to chromosomes
(kinetochore) [FIG.] [FIG.]
• Metaphase: chromosomes in equatorial position
• Anaphase: separation of sister chromatids → loosened chromatids
go towards the poles of mitotic spindle [FIG.] [FIG.]
• Telophase: reintegration of nuclear envelopes
[FIG.] [FIG.]
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Structure and function of mitotic spindle: 3 types of microtubules
(kinetochore m., polar m., astral m.) [FIG.]
Chromozome segregation by mitotic spindle:
• anaphase A
• anaphase B [FIG.]
Meiosis: production of hapliod gametes (in animals)
genetic recombination is accomplished during meiosis
Meiotic cell cycle: meiosis I
meiosis II
[FIG.]
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Structure and function of mitotic spindle: 3 types of microtubules
(kinetochore m., polar m., astral m.) [FIG.]
Chromozome segregation by mitotic spindle:
• anaphase A
• anaphase B [FIG.]
Meiosis: production of hapliod gametes (in animals)
genetic recombination is accomplished during meiosis
Meiotic cell cycle: meiosis I
meiosis II
[FIG.]
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Structure and function of mitotic spindle: 3 types of microtubules
(kinetochore m., polar m., astral m.) [FIG.]
Chromozome segregation by mitotic spindle:
• anaphase A
• anaphase B [FIG.]
Meiosis: production of hapliod gametes (in animals)
genetic recombination is accomplished during meiosis
Meiotic cell cycle: meiosis I
meiosis II
[FIG.]
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6. CELL DIVISION (CYTOKINESIS):
Cytokinesis mostly starts during mitotic anaphase.
Cytokinesis: enables approximately equal division of parental cell
components for two daughter cells (together with nuclei
also organelles, cytosol).
New cellular boundary is formed at the equatorial plate of mitotic
spindle.
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Mechanisms of cytokinesis:
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Animal cells: process of cleavage (furrowing) (contractile ring,
requirement for new plasma membrane) [FIG.] [FIG.]
Cells of higher plants: new cell boundary is formed as cell plate
(phragmoplast)
Algae and fungi: invagination of plasma membrane
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Mechanisms of cytokinesis:
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Animal cells: process of cleavage (furrowing) (contractile ring,
requirement for new plasma membrane) [FIG.] [FIG.]
Cells of higher plants: new cell boundary is formed as cell plate
(phragmoplast)
Algae and fungi: invagination of plasma membrane
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7. DOUBLING OF FUNCTIONAL CAPACITIES
OF THE CELL:
precise duplication of nuclear DNA vs. doubling of other cell components
• Synthesis of proteins and RNA
• Duplication of organelles
Synthesis of proteins and RNA: linear growth of protein amount during
cell cycle, ribosomes
Duplication of organelles:
• Simple membrane organelles: endoplasmic reticulum, Golgi apparatus
• Complex „cell like“ organelles: mitochondria, chloroplasts [FIG.]
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8. RESTING CELLS:
Resting cells (quiescent cells) = G0 cells = cell in G0 fázi
Transition G1 → G0 & G0 → G1: connected with changes in cell
physiology and it requires certain time
period [FIG.]
Physiological characteristics of G0 cells: G0 cells vs. G1 cells, Myc
protein level
Transition to G0 phase:
• G0 phase of stem cells
• Permanent transition to G0 phase is connected with the transition to
terminal differentiation stages
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8. RESTING CELLS:
Resting cells (quiescent cells) = G0 cells = cell in G0 fázi
Transition G1 → G0 & G0 → G1: connected with changes in cell
physiology and it requires certain time
period [FIG.]
Physiological characteristics of G0 cells: G0 cells vs. G1 cells, Myc
protein level
Transition to G0 phase:
• G0 phase of stem cells
• Permanent transition to G0 phase is connected with the transition to
terminal differentiation stages
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LITERATURE:
• Alberts B. et al.: Essential Cell Biology. Garland Science. New York
and London, pp. 609-646, 2010.
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