ch.18 Flashcards
Each parental cell gives rise to two _______ cells on completion of a cycle of cell division.
daughter
Eukaryotic cells progression through the cell cycle is controlled by what?
protein kinases
Defects in cell cycle regulations is a common cause of what?
the abnormal proliferation of cancer cells
The division cycle of most cells consists of 4 coordinated processes, what are they?
- cell growth
- DNA replication
- distribution of the duplicated chromosomes to daughter cells
- cell division
In prokaryotes, chromosomes is ______ and the daughter DNA is separated into the two daughter cells.
duplicated
What are the 4 cell cycle phases in eukaryotes?
M, G1, S, and G2
What is the M phase?
mitosis (nuclear division)
The M phase usually ends with what?
cell division (cytokinesis)
What is Interphase?
period between mitoses
What is interphase divided into?
G1, S, and G2
What is G1 phase?
- Interval between mitosis and DNA replication
- The cell is metabolically active and growing
What happens in S phase?
DNA replication
What happens in G2 phase?
- cell growth continues
- proteins are synthesized in preparation for mitosis
Early embryos may have cell cycles of ____ minutes
30
In early embryos, there is no what?
no growth (G1 or G2) phase
Animal cells in ____ are diploid.
G1
diploid = _____ DNA content
2n
In S phase, replication increases the DNA content to ____
4n
How can DNA content be determined?
by incubation of cells with a fluorescent dye that binds to DNA
What is fluorescence intensity of individual cells measured in?
a flow cytometer or fluorescence-activated cell sorter
The progression of cell division is regulated by what?
extracellular and internal signals
What are the control points that regulate cellular processes?
growth, DNA replication, mitosis
What is a major control point?
START
what does START control?
controls progression from G1 to S
What happens once cells pass START?
committed to entering S phase and undergoing one division cycle
What is passage through START highly regulated by?
external signals, such as nutrient availability and cell size
What happens if there is a shortage of nutrients?
yeast cells can arrest the cycle at START and enter a resting phase
Yeast cells must reach a minimum ____ to pass START.
size
Small daughter cells of budding yeasts spend a longer time in ___ and grow more than the large mother cell.
G1
Passing through the restriction point commits the cell to what phases?
S and M phase
If appropriate growth factors are not present in G1, what happens?
Progression stops at the restriction point and cells enter G0
What is G0?
a resting stage
Skin fibroblasts are arrested in G0 until stimulated by what?
platelet-derived growth factor to proliferate and repair wound damage
What is the cell cycle that’s controlled by transition from G2 to M, the point at which cell size and nutrient availability are monitored?
the fission yeast schizosaccharomyces pombe cell cycle
Cell cycle control in G2 also occurs in animal _____
oocytes
How long do vertebrate oocytes remain arrested in G2 for?
long periods (decades in humans)
In vertebrate oocytes, progression to M phase is triggered by what?
hormonal stimulation
Coordination of the cell cycle phases is dependent on a series of cell cycle _____
checkpoints
What do cell cycle checkpoints do?
prevent entry into the next phase until events of the preceding phase have been completed
DNA damage checkpoints ensures what?
- that damaged DNA is not replicated and passed on to daughter cells
- cell cycle is arrested until DNA is repaired or replicated
What does the spindle assembly checkpoint do?
stops mitosis at metaphase if chromosomes are not properly aligned on the spindle
What triggers the major eukaryotic cell cycle transitions?
a conserved set of protein kinases
The studies of frog oocytes contributed to identification of what?
frog oocytes are arrested in G2 until hormonal stimulation triggers entry into M phase
What was cytoplasmic factor was responsible for the study of frog oocytes discovery?
maturation promoting factor (MPF)
MPF is also present in what?
somatic cells
MPF incudes what?
entry into M phase
MPF appeared to act as what?
a general regulator of the transition from G2 to M
The genetic analyses of yeast determined what?
temperature-sensitive mutants that were defective in cell cycle progression
cell division cycle mutants (cdc) genes are required for what?
passage through START and entry into mitosis
What do cell division mutants (cdc) do?
encode protein kinases
what is Cdk1?
the protein kinase that is a cell cycle regulator conserved in all eukaryotes
Protein synthesis in early sea urchin embryos discovered what?
two proteins (cyclins) that accumulate throughout interphase but rapidly degrade at the end of mitosis
When the 3 experimental approaches to cell cycle regulators converged, how were the components determined to function together?
- MPF was composed of Cdk1 and cyclin B
- cyclin B is a regulatory subunit required for catalytic activity of the Cdk1 protein kinase
Research has established that _____ and _____ are members of protein families.
Cdk1 and cyclin B
In yeasts, what does Cdk1 control?
G2 to M transition in association with mitotic B-type cyclins
Cdk1 controls passage through START and entry into mitosis in association with what?
G1 cyclins or Cln’s
What does Cdk stand for?
cyclin-dependent kinases
Studies of Cdk’s and cyclins in genetically modified mice reveal high level of what?
plasticity
What does the high level of plasticity of Cdk’s and cyclins allow them to do?
compensate for the loss of either Cdk’s or cyclins
_____ is capable of substituting for all the other CDk’s
Cdk1
What are the 2 families of Cdk inhibitors in mammalian cells?
Ink4 and Cip/Kip
what are one link between growth factor signaling and cell cycle progression?
D-type cyclins
Growth factors stimulate cyclin D synthesis through what pathway?
the Ras/Raf/MEK/ERK pathway
Cyclin D1 is synthesized as longa as ____ ______ are present.
growth factors
Cyclin D1 is rapidly degraded due to what?
APC/C ubiquitin ligase
As long as growth factors are present through ____, Cdk4, 6/cyclin D complexes drive cells through the restriction point.
G1
Defects in cyclin D regulation could contribute to what?
the loss of growth regulation characteristic of cancer cells
Many human cancers arise as a result of defects in what?
cell cycle regulation
What is Rb?
a substrate protein of Cdk4, 6/cyclin D complexes
What substrate protein is frequently mutated in many human tumors?
Rb
What was Rb first identified in?
retinoblastoma
Rb is the prototype _____ _____ gene
tumor suppressor
The inactivation of Rb leads to what?
tumor development
Proteins encoded by tumor suppressor genes act as what?
brakes that slow down cell cycle progression
In G0 or early G1 \, Rb binds to what?
E2F transcription factors
When Rb binds to E2F, what does it do?
suppresses expression of genes involved in cell cycle progression
Progression through the restriction point is mediated by the activation of what?
Cdk2/cyclin E complexes
In G0 and early G1, Cdk2/cyclin E is inhibited by what?
p27 (Cip/Kip family)
How is the inhibition of Cdk2 relieved?
by multiple mechanisms as cells progress through G1
What reduces transcription and translation of p27?
growth factor signaling via Ras/Raf/MEK/ERk and PI 3-kinase/Akt pathways
When Cdk2 becomes activated, it phosphorylates ____ and targets it for ubiquitylation.
p27
What is inhibited by Cdk2?
APC/C ubiquitin ligase
When are high levels of cyclins maintained through S and G2?
when APC/C ubiquitin ligase is inhibited by Cdk2
what initiates S phase by activating DNA synthesis at replication origins?
Cdk2/cyclin E
MCM helicase and origin recognition complex (ORC) proteins bind to what during G1?
replication origins
Cdk2/cyclin E activates the _____ by phosphorylating activating proteins.
ORC
What does the inhibition of APC/C (by Cdk2/CycE) lead to?
the activation of protein kinase DDK
What does the protein kinase DDK phosphorylate directly?
MCM proteins
What does the high activity of Cdk’s during S, G2, and M phases prevent?
MCM proteins from reassociating with replication origins
Pre-replication complexes can only reform when?
during G1 when Cdk activity is low
Cell cycle arrest at DNA damage checkpoints is mediated by what?
protein kinases ATM and ATR
ATM and ATR activate a signaling pathway that leas to what?
cell cycle arrest, DNA repair, and programmed cell death
What phosphorylates and inhibits Cdc25 phosphatases?
Chk1 and Chk2
What are requires to activate Cdk1 and Cdk2?
Cdc25 phosphatases
Inhibition of Cdk2 results in what?
cell cycle arrest in G1 and S
What does inhibition of Cdk1 result in?
arrest in G2
In mammalian cells, arrest is also mediated by what protein?
p53
p53 is phosphorylated by what?
ATM and Chk2
Increased levels of p53 leads to what?
induction of Cdk inhibitor p21
what does p21 inhibit?
Cdk2/cyclin E or A complexes
When Cdk2/cyclin E or A complexes are inhibited, what does that lead to?
cell cycle arrest
what gene is frequently mutated in about 50% human cancer?
p53
Around 100% of cancers involve a defect in the ____ pathway.
p53
loss of ____ prevents cell cycle arrest in response to DNA damage, so the damaged DNA is replicated and passed on to daughter cells.
p53
What happens in chromatin condensation?
phosphorylation of condensins and cohesins
what happens in nuclear envelope breakdown?
phosphorylation of lamins, nuclear pore complexes, and inner nuclear membrane proteins
what happens in fragmentation of golgi apparatus?
phosphorylation of golgi matrix proteins
What happens in spindle formation?
phosphorylation of centrosome, kinetochore, and microtubule-associated proteins
Golgi breakdown is mediated by phosphorylation of proteins by _____ and _____ kinases.
Cdk1 and Polo-like
Reorganization of the cytoskeleton and formation of the mitotic spindle results from what?
the dynamic instability of microtubules
What are centrosome maturation and spindle assembly are driven by?
Aurora and Polo-like kinases at the centrosomes
In M phase, microtubule turnover rate ______, resulting in depolymerization and shrinkage of the interphase microtubules.
increases
In M phase, the number of microtubules radiating from the centrosomes ________.
increases
In the M phase, the breakdown of the nuclear envelope allows spindle microtubules to what?
attach to chromosomes at the kinetochores
In M phase, chromosomes in prometaphase do what due to activity of microtubule motors at the kinetochore and centrosomes.
shuffle back and forth
In the M phase, the balance of forces acting on the chromosomes leads to what?
their alignment on the metaphase plate
What does the spindle consist of?
kinetochore, polar microtubules, astral microtubules, and chromosomal microtubules
At the spindle assembly checkpoint, progression to anaphase is mediated by activation of ________
APC/C ubiquitin ligase
The presence of even one unaligned chromosome is sufficient to prevent what?
activation of the APC/C
Unattached kinetochores leads to the assembly of the ________ _______ _______.
mitotic checkpoint complex (MCC)
In the M phase, once all chromosomes are aligned on the spindle, the inhibitory complex is no longer formed and APC/C is ______
activated
APC/C ________ cyclin B and securin.
ubiquitylates
Cyclin B and securin inactivates what?
Cdk1 and separase
What breaks the link between sister chromatids, allowing them to segregate and move to opposite spindle poles?
separase degrades cohesin
Separation of chromosomes during anaphase proceeds by the action of what?
motor proteins associated with the spindle microtubules
APC/C also triggers degradation of Aurora and Polo-like kinases, allowing the cell do what?
to exit mitosis and return to interphase
What triggers cytokinesis?
inactivation of Cdk1
Cytokinesis of yeast and animal cells is mediated by a _____ _____ of actin and myosin II filaments that forms beneath the plasma membrane
contractile ring
Ring formation is activated by ______ and _______ kinases.
Aurora and Polo-like
What pulls the plasma membrane inward?
Contraction of the actin-myosin filaments, eventually pinching the cell in half
In plant cells, how does cytokinesis proceed?
by formation of new cell walls and plasma membranes
In ______ _____, vesicles carrying cell wall precursors from the Golgi accumulate at the former site of the metaphase plate.
early telophase
In M phase, the vesicles fuse to form a membrane-enclosed disk, and polysaccharides form the matrix of a new _____ _____ (cell plate)
cell wall
Plasmodesmata between the daughter cells are formed as a result of what?
incomplete vesicle fusion
