Cell Cycle Flashcards
3 parts of the cell cycle
Chromosome replication and cell growth
chromosome segregation
cell division
mitosis
nuclear division
cytokinesis
cell division
Longest phase of cell cycle
interphase
Short phase of the cell cycle
M phase
Three phases of interphase
G1, S, G2
What occurs in S phase
DNA replication
A comparison of the cell cycles of fission yeasts and budding yeasts
Fission vs budding
The fission yeast has a typical eucaryotic cell cycle with G1, S, G2, and M phases. In contrast with what happens in higher eucaryotic cells, however, the nuclear envelope of
the yeast cell does not break down during M phase. The microtubules of the mitotic spindle (light green) form inside the nucleus and are attached to spindle pole bodies
(dark green) at its periphery. The cell divides by forming a partition (known as the cell
plate) and splitting in two. The condensed mitotic chromosomes (red) are readily visible
in fission yeast, but are less easily seen in budding yeasts. (B) The budding yeast has
normal G1 and S phases but does not have a normal G2 phase. Instead, a microtubule based spindle begins to form inside the nucleus early in the cycle, during S phase. In contrast with a fission yeast cell, the cell divides by budding.
Cell cycle at permissive low temperature
normal
Cell cycle at permissive high temperature
restricted to G1 phase
The morphology of budding
yeast cells arrested by a cdc mutation
In a normal population of proliferating
yeast cells, buds vary in size according to
the cell-cycle stage.
In a cdc15 mutant
grown at the restrictive temperature, cells
complete anaphase but cannot complete the exit from mitosis and cytokinesis. As a
result, they arrest uniformly with the large
buds, which are characteristic of late M
phase
Oocyte growth and egg cleavage in Xenopus
The oocyte grows without dividing for many months in the ovary of the mother
frog and finally matures into an egg
What happens after Xenopus fertilization
the egg cleaves very
rapidly—initially at a rate of one division cycle every 30 minutes—forming a
multicellular tadpole within a day or two. The cells get progressively smaller with
each division, and the embryo remains the same size.
Growth in Xenopus occurs when?
Growth starts only when
the tadpole begins feeding. The drawings in the top row are all on the same
scale (but the frog below is not)
the presence of an S-phase cell is evidence of
cell proliferation occurring
in response to damage
Analysis of DNA content with a
flow cytometer:
What are the key results?
Cells location and DNA content..
Most cells in G1 > G2 >S
DNA content G2 (2) > S > G1 (1)
The distribution of cells in
the case illustrated indicates that there are
greater numbers of cells in G1 phase than in G2
+ M phase, showing that G1 is longer than G2 +
M in this population.
those that
have an unreplicated complement of DNA and
are therefore in G1 phase, those that have a
fully replicated complement of DNA (twice the
G1 DNA content) and are in G2 or M phase, and
those that have an intermediate amount of DNA
and are in S phase
The control of the cell
cycle.
The essential processes of the cell cycle—such as DNA replication, mitosis,
and cytokinesis—are triggered by a cellc ycle control system.
By analogy with a
washing machine, the cell-cycle control
system is shown here as a central arm—
the controller—that rotates clockwise,
triggering essential processes when it
reaches specific points on the outer dial.
Three checkpoints in
the cell-cycle control system
G1, G2, Metaphase Information about the completion of cell-cycle events, as well as signals from the environment, can cause the control system to arrest the cycle at specific checkpoints.
G1 checkpoint
when, question?
End of G1 to enter S
Is environment favourable
G2 checkpoint
when, question?
End of G2 to enter M
Is all DNA replicated?
Is environment favourable
M checkpoint
when, question?
Middle of metaphase
Are all chromosomes attached to the spindle?
Two key components of the cell- cycle control system
A complex of cyclin with Cdk acts as a
protein kinase to trigger specific cell-cycle
events. Without cyclin, Cdk is inactive`
What interacts with a single Cdk in the cell cycle?
S-cyclin, M-cyclin
complex: s-cdk, m-cdk
S-cdk triggers
DNA replication machinery
m-cdk triggers
mitosis machinery
Three D cyclins in mammals
cyclin D1, D2, and D3
Match Cyclin-CDK- complex - G1-Cdk - G1/S-Cdk - S-Cdk - M-Cdk
Cyclin in vertebrates
- E
- B
- A
- D
Match Cyclin-CDK- complex D - G1-Cdk E - G1/S-Cdk A - S-Cdk B - M-Cdk
3 states of Cdk
inactive, partially inactive, fully active
inactive Cdk
without cyclin bound, the active
site is blocked by a region of the protein called the T-loop (red)
Partially active Cdk
The binding of cyclin
causes the T-loop to move out of the active site, resulting in partial activation of the Cdk2
active Cdk
Phosphorylation of Cdk2 (by CAK) at a threonine residue in the T-loop further
activates the enzyme by changing the shape of the T-loop, improving the ability of the
enzyme to bind its protein substrates
inactive to partially active Cdk
binding of cyclin
partially active to active Cdk
Phosphorylation of Cdk2 (by CAK)
How is the cyclin–Cdk complex regulated by wee 1
turned off when the kinase Wee1
phosphorylates two closely spaced sites above the active site
Wee1
inhibitory phosphorylation
Removal of
these phosphates by the phosphatase Cdc25 results in activation of the
cyclin–Cdk complex
Regulation of cyclin–Cdk complex by a CKI
The inhibition of complex
The p27 binds to both the cyclin and Cdk in the complex, distorting the active
site of the Cdk. It also inserts into the ATP- binding site, further inhibiting the
enzyme activity
The control of proteolysis (CKI) occurs by
SCF and APC during the cell
cycle
The control of proteolysis by SCF
Degradation of CKI in proteosome
The phosphorylation of a target protein, such as the CKI shown, allows the protein
to be recognized by SCF, which is constitutively active. With the help of two additional
proteins called E1 and E2, SCF serves as a ubiquitin ligase that transfers multiple
ubiquitin molecules onto the CKI protein. The ubiquitylated CKI protein is then
immediately recognized and degraded in a proteasome.
The control of proteolysis by APC
Degradation of M-Cyclin in proteasome
M- cyclin ubiquitylation is performed by APC, which is activated in late mitosis by the
addition of an activating subunit to the complex. Both SCF and APC contain binding sites
that recognize specific amino acid sequences of the target protein.
S and G1 cell fusion
G1 phase nucleus immediately enters S phase
S phase nucleus continues DNA replication
S and G2 cell fusion
G2 phase nucleus stays in G2
S phase nucleus continues DNA replication
G1 and G2 cell fusion
G2 phase nucleus stays in G2
G1 phase nucleus enters S phase normally
The initiation of DNA
replication in cell cycle
The ORC remains associated with a
replication origin throughout the cell cycle.
In early G1, Cdc6 associates with ORC.
Aided by Cdc6, Mcm ring complexes then
assemble on the adjacent DNA, resulting in
the formation of the pre-replicative
complex. The S-Cdk (with assistance from
another protein kinase, not shown) then
triggers origin firing, assembling DNA
polymerase and other replication proteins
and activating the Mcm protein rings to
migrate along DNA strands as DNA
helicases. The S-Cdk also blocks
rereplication by causing the dissociation of
Cdc6 from origins, its degradation, and the
export of all excess Mcm out of the
nucleus. Cdc6 and Mcm cannot return to
reset an ORC-containing origin for another
round of DNA replication until M-Cdk has
been inactivated at the end of mitosis
The activation of M-Cdk
Cdk1 associates with M-cyclin as the levels of M-cyclin gradually rise. The resulting
M-Cdk complex is phosphorylated on an activating site by the Cdk-activating kinase
(CAK) and on a pair of inhibitory sites by the Wee1 kinase. The resulting inactive MCdk complex is then activated at the end of G2 by the phosphatase Cdc25.
Active m-CDK feedback loops
Cdc25 is further
stimulated by active M-Cdk, resulting in positive feedback.
M-Cdk also inhibits Wee1.
What is cdc25 stimulated by?
polo kinase
Concentrations of Cdk during cell cycle
do not change and exceed cyclin amounts
cyclin levels in G1
In late G1, rising G1/s-cyclin levels lead to formation of G1/S-cdk complexes that trigger proggestion through start transition
G1/S cyclin drops at start of S
cyclin levels in G2
m-CDK complexes form during G2 but are held in an inactive state
they are activated at the end of G2 and tigger entry into mitosis at G2/M transition
APC/C intiates
metaphase to anaphase transition
The structure and function of cohesins and condensins.
Related
Both proteins have two identical DNA- and ATP-binding domains at one end
and a hinge region at the other, joined by two, long, coiled-coil regions. This flexible structure is well suited for their role as DNA cross-linkers.
Cohesins cross-link
two adjacent sister chromatids, gluing them together.
Condensins mediate
intramolecular cross-linking to coil DNA in the process of chromosome
condensation
The triggering of sister-chromatid separation by the
APC
The activation
of APC by … leads to …
The activation
of APC by Cdc20 leads to the ubiquitylation and destruction of securin, which normally
holds separase in an inactive state
destruction of securin allows separase to
cleave a subunit of the cohesin complex holding the sister chromatids together
In early embryonic cell cycles,
Cdc20–APC activity rises at the
end of metaphase, triggering Mcyclin destruction
What keeps the Cdk activity supressed after mitosis which is required for a G1 phase?
the drop in M-Cdk activity in late mitosis leads to the activation of Hct1–APC (as well as to the accumulation of CKI proteins, not shown). This ensures a continued suppression of Cdk activity after mitosis, as required for a G1 phase.
The control of G1 progression by Cdk activity in budding
yeast
As cells exit from mitosis and inactivate M-Cdk, the resulting increase in
Hct1 and Sic1 activities results in stable Cdk inactivation during G1. When
conditions are right for entering a new cell cycle, the increase in G1-Cdk
and G1/S-Cdk activities leads to the inhibition of Sic1 and Hct1 by
phosphorylation, allowing S-Cdk activity to increase
What are the mehcnisms controlling S phase intiation in animal cells?
G1-Cdk activity initiates Rb phosphorylation –> inactivated Rb
Freeing E2F
E2F acts back to stimulate the transcription of its own gene, forming another
positive feedback loop
Aperance of G1/S-cdk and S-cdk is a positive feedback loop
What happens to the mass of cell with/without nutritional cell cycle control
If cell division continued at an unchanged rate when cells were starved and stopped growing, the daughter cells produced at each division would become progressively smaller respond to some forms of nutritional deprivation by slowing the rate of progress through the cell cycle so that the cells have more time to grow. As a result, cell size remains unchanged or is reduced slightly
How does yeast cells coordinate cell growth?
G1-cyclin bind to DNA bound proteins
once all are bound, the free G1-cyclin is able to bind to Cdk and proceed into S phase
How DNA damage
arrests the cell cycle in G1
When DNA is damaged, protein
kinases that phosphorylate p53 are
activated
p53 usually bound to Mdm2 and causes destruction
phosphorylation blocks binding and causes high tranlation of gene that encodes CKI
CKI inactivated G1/S-Cdk and S-CDK, arresting the cell in G1
CAK
phosphoylates an activiting site in Cdk
Wee1
phosphorylated inhibitory sites in Cdks, involved in controlling entry to mitosis
Cdc25 phosphatase
removes inhibitory phosphates from Cdks
- cdc 25A, B, C
- Cdc25C is the activator of cdk1 a the onset of mitosis
Sic1
supresses cdk activity in G1, phosphorylation by cdk1 triggers it destruction
p27
supresses G1/s-Cdk and S-cdk activities in G1
helps cells to withdraw from cell cycle
p21
SUPRESSES G1.S-CDK, s-cdk activities following DNA damage in G1
Why is the tail lost from the tadpole to frog
undergo apoptosis in tail due to stimulated by an increase in thyroid hormone in the blood
The binding of mitogens to cell-surface
receptors leads to the activation of
Ras
and a MAP kinase cascade
Ras
and a MAP kinase cascade activation results in
increased production of
the gene regulatory protein Myc
what does Myc increase
transcription of several
genes, including the gene encoding cyclin
D and a gene encoding a subunit of the
SCF ubiquitin ligase. The resulting
increase in G1-Cdk and G1/S-Cdk
activities promotes Rb phosphorylation and
activation of the gene regulatory protein
E2F, resulting in S-phase entry
usually functions as a heterodimer
MYC leads to increased ___ activity which leads to entry into _____
E2F
S phase
Abnormally high levels of Myc cause the activation of
p19ARF, which binds and inhibits
Mdm2 and thereby causes increased p53 levels
Depending on the
cell type and extracellular conditions, p53 then causes either cell-cycle arrest or
apoptosis.
activation of cell- surface
receptors leads to the
activation of … which promotes…
activation of cell- surface receptors leads to the activation of PI 3-kinase, which promotes protein synthesis, at least partly through the activation of eIF4E and S6 kinase. Growth factors also inhibit protein breakdown (not shown) by poorly understood pathways.
Why do some nerve cells apoptose
The number of nerve cells is much greater than target cells and thus some receive insufficient survival factors –> apoptosis
Two ways
in which survival factors suppress
apoptosis
the binding
of some survival factors to cell surface receptors leads to the activation of various protein
kinases, including protein kinase B
(PKB), that phosphorylate and inactivate the Bcl-2 family member
Bad.
When not phosphorylated, Bad promotes apoptosis by binding and inhibiting Bcl-2. Once phosphorylated, Bad dissociates, freeing Bcl-2 to suppress apoptosis. As indicated, PKB also suppresses death by phosphorylating and thereby inhibiting gene regulatory proteins of the Forkhead family that stimulate the transcription of genes that encode proteins that promote apoptosis.
What does ploidy affect
chromosomes
and size
as n increases, size increases too
