Cell Cycle Flashcards

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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
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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
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6
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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
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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
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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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15
Q

Cyclin-Cdk complex pairs

A
16
Q

Phospholipid

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19
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Phospholipid

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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

20
Q
A

Cdk activity can be
suppressed by inhibitory
phosphorylation and Cdk
inhibitor proteins (CKIs)

20
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21
Q

Cell cycle + cyclin-Cdks + key actions

A
21
Q

S-Cdk initiate DNA replication

A

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

21
Q
A
  • 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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24
Q

Control of cell growth

A

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

25
Q
A

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

26
Q

Mitogens stimulate G1-Cdk and G1/S-Cdk

A

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.

27
Q

DNA damage arrests the cell cycle in G1

A
  • 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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29
Q

Meiosis vs. Mitosis

A

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

30
Q
A

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

31
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31
Q

Crossing over during prophase I of meiosis I

A

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

32
Q

Meiosis vs. Mitosis

A
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