Cell Cycle Flashcards

1
Q

Learning Outcomes

A
  • Understand the concept of cell cycle and cell division
  • Understand the main checkpoints in cell cycle
  • Describe the roles of cyclins and Cdks
  • Describe the differences in meiosis from mitosis
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2
Q

Cell cycle

A

Only way to make a new cell is to duplicate a cell that
already exists
Cycle of duplication – cell cycle – essential for
reproduction, development, growth and homeostasis
If cell cycle not working, adult body can die in a few
days after a high dose x-ray

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2
Q

Reading:

A
  • Alberts et al. Molecular Biology of the Cell, Ch17
  • Alberts et al. Essential Cell Biology, Ch18
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2
Q

Cell cycle can be studied in various ways

A

Human cell culture provide an excellent system for
molecular and microscopic exploration
Cell-cycle control is very similar in all eukaryotes and
also well conserved over evolution (human cells to
yeast cells)

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3
Q
A

Main purpose – passing on the same genetic information
to the next generation (producing 2 genetically identical
daughter cells during mitosis) – need to be tightly
controlled and checked!
Other things also need to be duplicated e.g., organelles
and macromolecules otherwise, daughter cells will get
smaller

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4
Q
A

S phase can be studied by
utilizing bromodeoxyuridine
(BrdU), artificial thymidine
analog (ATGC)

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4
Q

4 phases of cell cycle (eukaryotic cell)

A
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5
Q
A
  • G1, S, G2 and M phases
    (G = Gap, S = DNA Synthesis and
    M = Mitosis)
  • G1,S, and G2 = interphase
  • Cell type dependent but can be ~
    24 hours – M phase = 1 hour and S
    = 10-12 hours
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6
Q
A
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6
Q
A
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7
Q
A

M (Mitosis) phase
* ~ 1 hour
* Mitosis (nuclear division) + cytokinesis (cell division) L#33

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8
Q
A

S (Synthesis) phase
* 10-12 hours
* DNA replication
* Highly accurate otherwise
mutation

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8
Q
A

G1 (Gap 1) phase
* fixed duration
* Synthesis of cell constituents
except DNA

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8
Q
A

G2 (Gap 2) phase
* fixed duration
* Growth of cell parts for the
division
* G2/M checkpoint – DNA
damage / correct replication

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9
Q

Cell-cycle control system

A

There are so many steps critical for a successful cell
division (a result of one cell cycle)
Main 3 checkpoints - decide whether to commit further
* G1/S checkpoint – restriction point (favorable env.?)
* G2/M checkpoint – DNA replication
* M checkpoint (spindle-assembly) – separation of DNA

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9
Q
A

G0 (Gap 0) phase
* If everything good, G1 can go to S without G0
* If No by G1/S checkpoint, cells rest at G0
* may re-enter cell cycle again e.g., liver cells upon damage

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10
Q

Cell-cycle control system

A

There are so many steps critical for a successful cell
division (a result of one cell cycle)
Main 3 checkpoints - decide whether to commit further
* G1/S checkpoint – restriction point (favorable env.?)
* G2/M checkpoint – DNA replication
* M checkpoint (spindle-assembly) – separation of DNA

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11
Q

Cyclin and cyclin-dependent protein kinase (Cdk)

A

Cyclin - cycle of synthesis and degradation in each cell cycle
Cdk – constant and dependent on cyclin
Cyclin-Cdk complex activation is the key

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11
Q
A
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12
Q
A

Rise and fall of cyclins control cell cycle
e.g, increased M-Cdk at G2/M increases phosphorylation of proteins that controls 1)
chromosome condensation, 2) nuclear-envelope breakdown, 3) spindle assembly
and other events (in Lecture #33)

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13
Q
A
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14
Q

Cyclin and cyclin-dependent protein kinase (Cdk)

A

Cyclin - cycle of synthesis and degradation in each cell cycle
Cdk – constant and dependent on cyclin
Cyclin-Cdk complex activation is the key

Rise and fall of cyclins control cell cycle
e.g, increased M-Cdk at G2/M increases phosphorylation of proteins that controls 1)
chromosome condensation, 2) nuclear-envelope breakdown, 3) spindle assembly
and other events (in Lecture #33)

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Cyclin-Cdk complex pairs
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Phospholipid
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Phospholipid
Activation of cyclin-Cdk complex A. In absence of cyclin, the active site in CdK is partly obscured by a protein loop(like a stone blocking the entrance to a cave) B. Cyclin binding cause the loop to move away from the active site – partial activation of Cdk enzyme C. Cdk-activating kinase (CAK) phosphylate an amino acid near the entrance of Cdk active site – conformational change that increase the activity
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Cdk activity can be suppressed by inhibitory phosphorylation and Cdk inhibitor proteins (CKIs)
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Cell cycle + cyclin-Cdks + key actions
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S-Cdk initiate DNA replication
Replication must occur with extreme accuracy to minimise the risk of mutations * Every nucleotide (A, T, G, C) must be copied once, and only once
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* DNA replication begins at origin of replication – numerous locations in every chromosomes * Licensing of replication origins – when inactive DNA helicases loaded onto the replication origin forming prereplicative complexes * S-Cdk – activate DNA replication with other proteins
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Control of cell growth
The size of an organ depends on its total cell mass – number of cells and their size Tightly controlled cell growth, division and survival By intracellular programs and by extracellular signal * Mitogens – primarily by triggering a wave of G1/S-Cdk (removing of blocking cell cycle) * Growth factors – promoting synthesis of proteins and macromolecules by inhibiting degradation * Survival factors – suppressing apoptosis
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In the absence of a mitogenic signal to proliferate, Cdk inhibition in G1 is maintained and progression into a new cell cycle is blocked. Specialised nondividing state, G0
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Mitogens stimulate G1-Cdk and G1/S-Cdk
Upon mitogen binding to the receptor on the surface of plasma membrane, GTPase RAS activate mitogen-activated protein kinase (MAP kinase) cascade. * Myc (transcription regulatory protein) activate G1-Cdk which phosphorylate Rb (retinoblastoma) proteins leading activation of E2F proteins (promoting transcription activity – key for DNA replication). * With following positive feedback loops, DNA synthesis can be efficiently accomplished.
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DNA damage arrests the cell cycle in G1
* G1/S-Cdk and S-Cdk need to be activated to pass G1/S checkpoint but if DNA is damaged, cell cycle should not proceed to S phase * When DNA damage phosphorylate p53, activation of p53 transcribe p21 gene * Translation of p21 mRNA to p21 protein (repressor protein) inhibit activity of G1/S-Cdk and S-Cdk * When DNA damage is repaired, p53 level drops (degradation), cyclin-Cdk is no longer inhibited and blocked G1/S checkpoint is removed
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Meiosis vs. Mitosis
Meiosis * Generation of gametes (e.g., Egg and sperms) to carry only a single copy of parent’s chromosome * Diploid (carrying chromosome pairs) to haploid (carrying only 1 chromosome of pairs) * Sexual reproduction cycle ends when 2 haploids (a sperm and egg) fuse to form a diploid zygote, which can from a new individual * 2 cell divisions
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Mitosis * Generation of 2 identical daughter cells * 2 daughter cells will have the same number of chromosomes as a parent cell (diploid to diploid) * A single cell division * For multicellular eukaryotic organism – tissue growth and replacement of cells * For single cell eukaryotic organism – asexual reproduction
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Crossing over during prophase I of meiosis I
Crossing over * Only in meiosis * Same type of chromosomes lined up during prophase I * Chiasma forms between a pair of homologous chromosomes by crossover of non-sister chromatids * Switch (exchange of genetic materials) can happen in non-sister chromatids of a homologous chromosomes * Allows new combinations of genetic materials – genetic variation
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Meiosis vs. Mitosis
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