Cell Cycle Flashcards
Learning Outcomes
- 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
Cell cycle
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
Reading:
- Alberts et al. Molecular Biology of the Cell, Ch17
- Alberts et al. Essential Cell Biology, Ch18
Cell cycle can be studied in various ways
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)
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
S phase can be studied by
utilizing bromodeoxyuridine
(BrdU), artificial thymidine
analog (ATGC)
4 phases of cell cycle (eukaryotic cell)
- 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
M (Mitosis) phase
* ~ 1 hour
* Mitosis (nuclear division) + cytokinesis (cell division) L#33
S (Synthesis) phase
* 10-12 hours
* DNA replication
* Highly accurate otherwise
mutation
G1 (Gap 1) phase
* fixed duration
* Synthesis of cell constituents
except DNA
G2 (Gap 2) phase
* fixed duration
* Growth of cell parts for the
division
* G2/M checkpoint – DNA
damage / correct replication
Cell-cycle control system
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
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
Cell-cycle control system
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
Cyclin and cyclin-dependent protein kinase (Cdk)
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)
Cyclin and cyclin-dependent protein kinase (Cdk)
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)
Cyclin-Cdk complex pairs
Phospholipid
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
Cdk activity can be
suppressed by inhibitory
phosphorylation and Cdk
inhibitor proteins (CKIs)
Cell cycle + cyclin-Cdks + key actions
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
- 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
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
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
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.
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
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
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
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
Meiosis vs. Mitosis
