Cell cycle (Mitosis) Flashcards
At prophase
- the replicated chromosomes, each
consisting of two closely associated sister chromatids, condense - Outside the nucleus, the mitotic spindle
assembles between the two centrosomes, which have replicated and moved apart. - In diploid cells, there would be
two copies of each chromosome present
At prometaphase
- starts abruptly with the breakdown of the nuclear envelope
- Chromosomes can now attach to spindle
microtubules via their kinetochores and undergo active movement.
At metaphase
- the chromosomes are aligned at the equator of the spindle, midway between
the spindle poles. - The kinetochore microtubules attach sister chromatids to opposite poles of the
spindle.
At anaphase
- the sister chromatids synchronously separate to form two daughter chromosomes,
and each is pulled slowly toward the spindle pole it faces. - The kinetochore microtubules get shorter,
and the spindle poles also move apart; both
processes contribute to chromosome segregation.
During telophase
- the two sets of daughter chromosomes arrive at the poles of the spindle and decondense.
- A new nuclear envelope reassembles around each set, completing the formation
of two nuclei and marking the end of mitosis. 3. The division of the cytoplasm begins with contraction of the contractile ring
During cytokinesis
- the cytoplasm is divided in two by a contractile ring of actin and myosin
filaments, which pinches the cell in two to create two daughters, each with
one nucleus.
induce the assembly of the mitotic spindle and ensure that each sister chromatid in a pair is attached to the opposite pole of the spindle
M-Cdk
M-Cdk induce the assembly of the ____ ____ and and ensure that each sister chromatid in a pair is attached to the ____ ____ of the ____
mitotic spindle
opposite pole of the spindle.
triggers chromosome condensation
M-Cdk
promotes the breakdown of the nuclear envelope and rearrangements of the actin cytoskeleton and the Golgi apparatus
M-Cdk
2 phosphorylation of specific proteins
Polo-like kinase (Plk)
Aurora kinases
required for the normal assembly of a
bipolar mitotic spindle
Polo-like kinase (Plk)
2 types of Aurora kinases
A
B
helps control proteins that govern the
assembly and stability of the spindle
A
controls attachment of sister chromatids to the spindle
B
begins with the accumulation of M-cyclin
M-Cdk activation
stockpile of M-Cdk
Cdk-activating kinase (CAK) and
inhibitory protein kinase Wee1
removes inhibitory phosphatase that
restrain M-Cdk
activation of phosphatase Cdc25
activation of phosphatase Cdc25 removes inhibitory phosphatase that
restrain _-___
M-Cdk
inhibitory activity of the kinase ____ is
suppressed
Wee1
suggests that M-Cdk activation in mitosis involves positive feedback loops
ability of M-Cdk to activate its own activator (Cdc25) and inhibit its own inhibitor (Wee1)
activator of M-Cdk
Cdc25
inhibitor of M-Cdk
Wee1
chromatids are compacted
chromosome condensation
two sisters are resolved into distinct, separable units
sister-chromatid resolution
condensation and resolution of sister chromatids depend on a five-subunit protein complex called
condensin
holds sister chromatids
Condensin
What does condensin contains?
two SMC subunits plus three non-SMC
subunits
Condensin may form a ______ structure that
somehow uses the energy provided by ATP hydrolysis to promote the _____
and _____of sister chromatids.
ringlike
compaction and resolution
depends on mitotic spindle
chromosome segregation
triggers the assembly of the spindle
early in mitosis
M-Cdk
Spindle formation in animal cells depends
largely on the ability of motor proteins to organize ?
bipolar array of microtubules
overlapped with the plus ends of microtubules from the other pole
interpolar microtubules
attached to sister-chromatid pairs at large protein structures called kinetochores
kinetochore microtubules
radiate outward from
the poles and contact cell cortex
astral microtubules
consists of a cloud of pericentriolar matrix that surrounds a pair of centrioles
centrosome
Each centrosome
consists of a cloud of amorphous material called the
pericentriolar matrix
pericentriolar matrix contains a
variety of proteins, including ______-____ motor proteins, _____-____ proteins that link the motors to the centrosome, ____ proteins, and components of the ___-____ ____ ___
microtubule-dependent
coiled-coil
structural
cell-cycle control system.
contains γ-tubulin ring complexes
pericentriolar matrix
microtubule-dependent motor protein depends on?
kinesin-related proteins and dyneins
usually move toward the plus end
of microtubules
kinesin-related proteins
move toward the minus end
dyneins
Four major types of motor proteins
kinesin-5, kinesin-14, kinesins-4/10,
and dynein
move toward the plus ends of the microtubules, they slide the two antiparallel microtubules past each other toward the spindle poles, pushing the
poles apart
kinesin-5
are minus-end directed motors; cross-link antiparallel interpolar microtubules at the spindle midzone and tend to pull the poles together
kinesin-14
- minus-end directed motors
- cross-link antiparallel interpolar microtubules at the spindle midzone and tend to pull the poles together
kinesin-14
-also called chromokinesins
-plus-end directed motors that associate with chromosome arms and push the attached chromosome away from the pole
kinesin-4/10
kinesin-4/10 are also called ?
chromokinesins
- minus-end directed motors
- motors pull the spindle poles toward the cell cortex and away from each other
dynein
mitotic spindle must have two poles
bipolarity of spindle
enters mitosis with a pair of centrosomes
depends on centrosome
Spindle formation depend on the ability of mitotic chromosomes to ____ and ____microtubules and on the ability of motor proteins to organize
microtubules into a ___array
nucleate
stabilize
bipolar
centrosome duplicates when the cell
enters the?
cell cycle – S phase
helps initiate centrosome
duplication
G1/S-Cdk
separate, and each nucleates the
formation of a single new centriole
two centrioles in the centrosome
two centrioles in the centrosome
separate, and each nucleates the
formation of a single new centriole, resulting in
two centriole pairs within an enlarged
pericentriolar matrix
mechanism of duplication use by both centrosome duplication and chromosome duplication
semiconservative mechanism of
duplication
must replicate once and only once per
cell cycle
Centrosomes
spindle assembly begins in?
early mitosis
pulled by dynein motor proteins that link ___ microtubules to the cell
cortex
astral
plus ends of the microtubules between the centrosomes interdigitate to
form the
interpolar microtubules
the number of γ-tubulin ring
complexes in each centrosome increases greatly, increasing the ability of the centrosomes to nucleate new microtubules, a process called
centrosome maturation
generally promote centrosome separation and
increase spindle length
dynein and kinesin-5 motors
phosphorylate kinesin-5 motors
M-Cdk and Aurora-A
located in the cytoplasm
centrosomes and microtubules
located in the nucleus
chromosomes
allowed the attachment of sisterchromatid pairs to the spindle
removal of nuclear membrane
begin when M-Cdk phosphorylates several subunits of the nuclear pore
complexes
Nuclear-envelope breakdown
M-Cdk also phosphorylates components of the
nuclear lamina
microtubules are either catastrophe or rescue
microtubule dynamic instability
switch from growth to shrinkage
catastrophe
shrinkage to growth
rescue
Signals ann abrupt change in the cell’s microtubules
Entry into mitosis
emanating from both centrosomes
larger number of shorter and more dynamic microtubules
half-life in microtubule decreases
prophase, prometaphase, metaphase
increase in microtubule instability, coupled with the increased ability
of centrosomes to nucleate microtubules results in remarkably dense and dynamic arrays of _____ _____ that are ideally suited for capturing _____ ______
spindle microtubules
sister chromatids
promote stability and
catastrophe factors that destabilize microtubule plus ends
microtubule-associated proteins (MAPs)
chromosomes play an active part in spindle
formation bycreating a local environment
that favors both
microtubule nucleation and
microtubule stabilization
bound to the chromatin
guanine nucleotide exchange factor
guanine nucleotide exchange factor (GEF) that is bound to chromatin ->
activated Ran-GTP – releases microtubule-stabilizing proteins
guanine nucleotide exchange factor (GEF) that is bound to chromatin ->activated Ran-GTP – releases microtubule-stabilizing proteins->
nucleation and stabilization of
microtubules around chromosomes
the ability of chromosomes to stabilize and
organize microtubules enables cells to form
bipolar spindles in the absence of
centrosomes
use this chromosome-based self-organization process to
form spindles
higher plants, animal oocytes, animal
embryos develop from eggs without
fertilization
second major step
in spindle formation
attachment of the array to the sister-chromatid pairs
a giant, multilayered
protein structure that is built at the
centromeric region of the chromatid
kinetochore
embedded head-on in specialized
microtubule attachment sites
plus ends of kinetochore microtubules
rod-shaped protein complex;
linking the microtubule to the
kinetochore
Ndc80
most initial attachments
unstable lateral attachments
unstable lateral attachments, in which _____attaches to the
side of the passing _____
kinetochore
microtubule
dynamic microtubule plus ends capture the ____ in the correct ___-__ orientation
Kinetochores
end-on
microtubules in the vicinity of the chromosomes become
embedded in the plus-end-binding sites of the kinetochore in the absence of?
absence of centrosome
Polymerization at plus-end-binding sites of the kinetochore then results in growth of the ______ away from the _____.
microtubules
kinetochore
sister chromatids in a pair attach to opposite poles of the mitotic spindle
bi-orientation
What prevents the attachment of both kinetochores to the same
spindle pole or the attachment of one kinetochore to both spindle poles?
sister kinetochores are constructed in a back-to-back orientation that reduces the likelihood that both kinetochores can face the same spindle
pole.
corrected by a
system of trial and error
incorrect attachments
highly unstable
and do not last
incorrect attachments
how does the kinetochore sense a correct
attachment?
tension
When a sister-chromatid pair is properly bi-oriented on the spindle, the two kinetochores are pulled in opposite directions by strong poleward forces. Sister-chromatid cohesion resists these poleward forces, creating high levels of tension within
the kinetochores
when both sister chromatids are attached
to the same spindle pole →
low tension
within the kinetochores
when both sister chromatids are attached
to the same spindle pole → low tension
within the kinetochores →
sends an
inhibitory signal that loosens the
attachment
tension-sensing mechanism depends on the
protein kinase ?
Aurora-B
depends on the
protein kinase Aurora-B
tension-sensing mechanism
generate the inhibitory signal that reduces the
strength of microtubule attachment in the
absence of tension
Aurora-B
phosphorylate some components at microtubule
attachment site →
decrease affinity for
microtubule plus end
initiates sister-chromatid separation by
ubiquitylating several mitotic regulatory
proteins and thereby triggering their
destruction
anaphase-promoting complex (APC/C)
anaphase-promoting complex (APC/C)initiates sister-chromatid separation by
_____ several mitotic ____
proteins and thereby triggering their
____
ubiquitylating
regulatory
destruction
cohesins hold sister
chromatids together
metaphase
loss of sister-chromatid
cohesion
anaphase
APC/C target ____ (inhibitory protein)
for destruction
securin
securin binds to and inhibits the activity
of a protease called
separase
separase cleave subunits of
cohesin
APC/C also targets the _- and _-____for destruction leading to Cdk inactivation
S- and M-cyclins
allows phosphatases to
dephosphorylate the many Cdk target
substrates in the cell, as required for the
completion of mitosis and cytokinesis
Cdk inactivation
blocks
progression through the metaphase-toanaphase transition
spindle assembly checkpoint
spindle assembly checkpoint mechanism ensures that cells do not enter _____
until all chromosomes are correctly bi-oriented on the ____ ___
anaphase
mitotic spindle
not properly attached kinetochore →
blocks Cdc20-APC/C activation
not properly attached kinetochore →
blocks Cdc20-APC/C activation →
blocks the metaphase-to-anaphase
transition
unattached kinetochore acts like
an enzyme that catalyzes a change in
the conformation of Mad2
Mad2
unattached kinetochore acts like
an enzyme that catalyzes a change in
the conformation of Mad2 →
can bind
and inhibit Cdc20–APC/C
sudden loss of sister-chromatid cohesion at
the onset of anaphase →
chromosome
segregation
initial poleward movement
of the chromosomes
anaphase A
Chromosome movement in anaphase A depends on a combination of the two
major poleward forces :
- microtubule depolymerization at the
kinetochore - microtubule flux- poleward
movement of the microtubules
separation of the spindle
poles themselves
anaphase B
the two sets of chromosomes are packaged into a
pair of daughter nuclei
telophase
disassembly of mitotic spindle → r
reformation of the nuclear
envelope
promotes spindle assembly,
chromosome condensation, and nuclear envelope breakdown
phosphorylation by M-Cdk
phosphorylation by M-Cdk promotes?
spindle assembly,
chromosome condensation, and nuclear envelope breakdown
spindle disassembly and the re-formation of
daughter nuclei
dephosphorylation
could be
triggered by the inactivation of Cdks, the activation of
phosphatases, or both
dephosphorylations and the completion of mitosis
dephosphorylations and the completion of mitosis could be
triggered by the
inactivation of Cdks, the activation of
phosphatases, or both
