Module 7: The Cell Cycle Part 2 (Cytokinesis, Meiosis, Control of Cell Division and Cell Growth, Cell Death) Flashcards
The final stage of the cell cycle, where the cytoplasm divides into two daughter cells.
Cytokinesis
When cells undergo mitosis without cytokinesis, they become __, containing multiple nuclei in a single cytoplasm.
multinucleated
What marks the beginning of cytokinesis on the cell surface?
appearance of a pucker or cleavage furrow
What structure is responsible for the physical separation of the cytoplasm?
contractile ring
The separation of sister chromatids during anaphase triggers the assembly of…
cytokinesis
contractile ring
Which proteins accumulate in the contractile ring during cytokinesis as the sister chromatids separate in anaphase? (2)
- Actin
- myosin II
What protein is responsible for the local formation of actin filaments in the contractile ring which facilitates the assembly of parallel arrays of linear, unbranched actin filaments?
cytokinesis
Formin
Overlapping arrays of __ and __ contract to generate the force that divides the cytoplasm in two.
cytokinesis
-actin; and
- myosin II filaments
- a structure that persists as a tether between the two daughter cells and contains the remains of the __.
- a large protein structure derived from antiparallel interpolar microtubules of the spindle midzone, tightly packed together within a dense matrix material.
cytokinesis (main answer, blank-2)
Midbody
- central spindle
- a small GTPase of the Ras superfamily that plays a critical role in cell division.
- controls the assembly and function of the contractile ring at the site of cleavage.
- promotes actin filament formation, myosin II assembly, and ring contraction at the cell cortex.
- activates formins and multiple protein kinases, including Rho-associated protein kinase (Rock).
RhoA
- Cytokinesis must occur only after the two sets of chromosomes are __ from each other.
- The __ must be placed between the two sets of daughter chromosomes.
- The correct timing and position depend on the __.
- fully segregated
- site of division
- mitotic spindle
- During anaphase, the spindle generates signals that initiate __ at a position midway between the spindle poles.
- The correct timing involves the __ of __, which depends on cyclin destruction in metaphase and anaphase.
- furrow formation
- dephosphorylation
- Cdk substrates
- the first model that explains how the mitotic spindle specifies the site of division
- Astral microtubules carry furrow-inducing signals.
Astral Stimulation Model
- the second model that describes the mitotic spindle’s role in specifying the site of division
- The spindle midzone, or central spindle, generates a furrow-inducing signal that specifies the site of furrow formation at the cell cortex.
Central Spindle Stimulation Model
- third model that outlines the mitotic spindle’s mechanism in specifying the division site
- The astral microtubules promote local relaxation of actin-myosin bundles at the cell cortex, with minimal relaxation at the spindle equator, thus promoting cortical contraction.
Astral Relaxation Model
- Higher-plant cells are enclosed by a semirigid (1)__.
- The cytoplasm is partitioned by the construction of a new cell wall called the (2)__, which forms between the two daughter nuclei.
- The formation of the (2)__ begins in (3)__ and is guided by the (4)__, which contains microtubules derived from the mitotic spindle.
cytokinesis in plants
1) cell wall
2) cell plate
3) late anaphase
4) phragmoplast
- Each daughter cell must inherit __ essential cell components, including membrane-enclosed organelles.
- Organelles can arise only by the growth and division of __.
- __ and __ are usually present in large enough numbers to double during each cell cycle.
cytokinesis in plants
- all
- preexisting organelles
- Mitochondria
- chloroplasts
What organelles?
- The __ is cut into two during cytokinesis.
- The __ is reorganized and fragmented during mitosis.
cytokinesis in plants
- Endoplasmic reticulum (ER)
- Golgi apparatus
A cell division is when cells divide to produce two daughter cells that differ in size, cytoplasmic contents, or both.
Asymmetric cell division
The mother cell must first segregate __ to one side and then position the plane of division so that the appropriate daughter cell inherits these components.
cell fate determinants
When cells undergo multiple rounds of nuclear division without intervening cytoplasmic division, it leads to the formation of a __, where many nuclei share a common cytoplasm.
syncytium
In which organism does the first 13 rounds of nuclear division occur without cytoplasmic division?
Drosophila (fruit fly) embryo
What is the advantage of multiple nuclear divisions without cytoplasmic division in early development?
greatly speeds up early development
During __, membranes are created around each nucleus in one round of coordinated cytokinesis.
cellularization
Name three types of cells that may undergo polyploidy or large cell formation. (3)
- megakaryocytes
- hepatocytes
- heart muscle cells
Generates genetically distinct offspring by mixing the genomes of two parents and reducing the chromosome number by half.
Meiosis
contain two homologs of each chromosome, one from each parent.
diploid cells
carry only a single copy of each chromosome, typical of gametes (sperm and egg).
haploid cells
When sperm and egg fuse, they form a __, a diploid cell with a complete set of chromosomes.
zygote
Meiosis produces __ (how many?) __ (what kind of cell?) daughter cells, each carrying a maternal or paternal chromosome copy.
- four
- haploid
Duplication of chromosomes occurs in preparation for division.
What phase?
S Phase
Meiosis involves __ successive rounds of __.
- two
- chromosome segregation
During meiosis I, what pair up and are segregated into two cells?
Homologous chromosomes (paternal and maternal)
No further DNA replication occurs, and sister chromatids are pulled apart and segregated.
Meisois II
Homologs __ and __ physically during meiosis, to ensure the maternal and paternal homologs are bi-oriented on the first meiotic spindle.
- recognize
- associate
A prolonged phase where homologous chromosomes begin pairing through interactions at specific pairing sites.
meiotic prophase I
A four-chromatid structure formed during meiosis I when homologous chromosomes pair up.
bivalent
Homolog pairs are locked together during meiosis through __, which stabilizes the bivalent structure.
homologous recombination
- The exchange of DNA between chromatids, where a segment of a chromatid becomes continuous with a segment of its homolog.
- They ensure accurate segregation of homologs and contribute to genetic diversity in offspring.
crossover
During meiosis, paired homologs are brought into close __ , aligning their structural axes (__).
- juxtaposition
- axial cores
juxtapstn-placing two opposing elements close together or side by side
A protein assembly that binds to a double-strand break in a chromatid, matches it to the DNA sequence in the nearby homolog, and helps reel in the partner chromosome.
recombination complex
The initial stage in homolog pairing, which leads to synapsis—the tight linking of homolog axial cores.
presynaptic alignment
__ form part of the __ mediates the tight linkage of homologous axial cores during synapsis
- Transverse filaments
- synaptonemal complex
A protein structure that stabilizes paired homologs during meiosis by tightly linking their axial cores.
synaptonemal complex
What are the five sequential stages of meiotic prophase? (5)
1) Leptotene
2) Zygotene
3) Pachytene
4) Diplotene
5) Diakinesis
Homologs condense and pair, and genetic recombination begins.
Prophase I
Leptotene
The synaptonemal complex begins to assemble at sites where homologs are closely associated, and recombination events occur.
Prophase I
Zygotene
The assembly of the synaptonemal complex is complete, and homologs are fully synapsed along their entire lengths.
Prophase I
Pachytene
The disassembly of synaptonemal complexes, accompanied by the condensation and shortening of chromosomes.
Prophase I
Diplotene
Segregation of homologs begins as chromosomes prepare for metaphase I.
Prophase I
Diakinesis
- the visible connections between nonsister chromatids of homologous chromosomes, resulting from individual crossover events during meiosis.
- stabilize homologous pairs (bivalents) and help ensure accurate segregation of homologs during meiosis I.
Chiasmata
Three features of meiosis I that distinguish it from mitosis:
1. Both __ in a homolog attach to the __ spindle pole in meiosis I.
2. __ generate a strong physical linkage between homologs, enabling their bi-orientation at the spindle equator.
3. Cohesion is removed during __ only from the __, not from the regions near the __ where kinetochores are located.
- sister kinetochores; same
- Crossovers
- anaphase I; chromosome arms; centromeres
A kinetochore-associated protein called __ protects centromeric cohesins by recruiting a phosphatase to remove phosphates, preventing separase activity.
shugoshin
Two primary functions of crossing-over during meiosis:
1. ___ for proper segregation during meiosis I.
2. Contributes to __ in gametes.
- Holds homologs together
- genetic diversity
Each pair of homologs is linked by about __ crossovers, with at least __ crossover forming between members of each homolog pair.
Crossing-over regulation in human homologs
- 2-3
- 1
DNA regions accessible to crossovers.
crossover “hot spots”
Regions like heterochromatin near centromeres and telomeres where crossovers are rare.
crossover “cold spots”
The presence of one crossover event inhibits another from forming nearby.
crossover interference
- Errors in chromosome segregation during meiosis significant because errors, such as (1)__, can lead to gametes lacking or having extra chromosomes, causing disorders like (2)__(__).
- (1)__ is also a major cause of (3)__ and (4)__ in humans.
1) nondisjunction
2) Down syndrome (trisomy 21)
3) spontaneous abortion (miscarriage)
4) mental retardation
Unique about meiotic arrest in human females:
- Meiosis I arrests in the diplotene stage for years, resuming only at __.
- Meiosis II is completed only after __.
- ovulation
- fertilization
- What fundamental processes determines organ and body size? (3)
- How are these processes regulated?
- Cell growth
- cell division
- cell survival
- By intracellular and extracellular signals.
Secreted proteins, proteins bound to the surface of cells, or components of the extracellular matrix.
extracellular signal molecules
Signal molecules that stimulate cell division and G1/S-Cdk activity.
Mitogens
Signal molecules that promote cell survival by suppressing apoptosis.
survival factors
A factor that has activities such as stimulating cell growth, division, or survival.
Growth factor
What is the relationship between cell growth and cell proliferation?
Cell growth = cell proliferation
What process do extracellular signal molecules activate apart from growth and survival?
Apoptosis
The rate of proliferation in unicellular organisms depend on the __.
availability of nutrients
Organisms that divides only when the organism needs more cells.
multicellular organisms
What type of signals do cells receive to stimulate division that are stimulatory extracellular signals?
mitogens
The first mitogen identified, which stimulates fibroblasts in culture to proliferate when provided with serum not when provided with plasma
platelet-derived growth factor (PDGF)
What types of cells does PDGF stimulate to divide? (3)
- Fibroblasts
- smooth muscle cells
- neuroglial cells
A growth factor that acts on epidermal cells and many other cell types, including epithelial and nonepithelial cells.
epidermal growth factor (EGF)
Only induces the proliferation of red blood cell precursors.
erythropoietin
Inhibitory extracellular signal proteins that inhibit proliferation.
transforming growth factor-β (TGFβ)
In the absence of a __, Cdk inhibition is maintained (G1), leading to a __ (specialized nondividing state).
- mitogenic signal
- G0 state
The cell-cycle control system is completely dismantled, and gene expression for Cdks and cyclins is permanently turned off, and cell division rarely occurs.
terminally differentiated G0 state
What can some cells do when damaged, such as liver cells?
Withdraw from and re-enter the cell cycle.
Mitogens control the rate of cell division by acting in the __ phase of the cell cycle.
G1
Signaling pathway initiated by a mitogen?
Mitogen
→ monomer __
→ activation of __ cascade
→ promote cell-cycle entry to __
→ increase expression of genes encoding __(__)
- GTPase Ras
- MAP kinase
- nucleus
- G1 cyclin (G1-Cdk)
The activation of the MAP kinase cascade lead to the production of __, such as __, which promote cell-cycle entry.
- transcription regulatory proteins
- Myc
It increases the expression of genes encoding G1 cyclins (G1-Cdk).
Myc
They bind to specific DNA sequences in the promoters of genes required for S-phase entry.
E2F proteins
An interaction between __ and members of the __ family inhibits E2F-dependent gene expression in the absence of mitogenic stimulation.
- E2F
- retinoblastoma protein (Rb)
What results to spontaneous chemical reactions in DNA, errors in DNA replication, exposure to radiation, or certain chemicals?
DNA damage
The cell-cycle control responds to DNA damage and arrests the cycle at the __ and __.
- Start
- G2/M transitions
The signaling pathway activated by DNA damage are __ and __, which phosphorylate __ and __, leading to the stabilization of __.
- ATM
- ATR
- Chk1
- Chk2
- protein p53
stimulates transcription of the gene encoding p21 (a CKI protein), which binds G1/S-Cdk and S-Cdk complexes to inhibit their activities and block entry into the cell cycle.
p53
In undamaged cells, p53 is highly unstable and present at very low concentrations due to __, which acts as a ubiquitin ligase targeting p53 for destruction.
Mdm2
__ and __ phosphorylate the Cdc25 family of protein phosphatases.
- Chk1
- Chk2
When a replication fork fails during DNA replication, low levels of DNA damage occur, and accumulation of genetic damage in cells lacking the DNA damage response increases the frequency of __.
cancer-promoting mutations
Mutations in the __ are found in half of all human cancers, allowing cancer cells to accumulate mutations more readily.
p53 gene
a defect in ATM, making individuals very sensitive to X-rays and leading to increased rates of cancer.
DNA damage
Ataxia telangiectasia
It is the phenomenon where many human cells divide a limited number of times before undergoing a permanent cell-cycle arrest.
replicative cell senescence
undergo changes that result in progressive shortening with each cell division when telomerase is not produced.
Telomeres
synthesizes telomeres and promotes the formation of protein cap structures that protect chromosome ends.
Telomerase
When cells do not produce telomerase, their telomeres become __ with every cell division, and their protective protein caps progressively __.
- shorter
- deteriorate
Exposed chromosome ends are sensed as __, activating a __ arrest.
- DNA damage
- p53-dependent cell-cycle
Most cancer cells have regained the ability to produce __, allowing them to maintain telomere function as they proliferate.
telomerase
Genes that, when mutated or overexpressed, contribute to the development and progression of cancer.
cancer-promoting genes
A mutation in __ can lead to a permanently overactive form, resulting in constant stimulation of Ras-dependent signaling pathways.
GTPase Ras
The overexpression of __ stimulates excessive cell growth and proliferation.
Myc
a cyclin-dependent kinase inhibitor protein that, when produced excessively, inhibits Mdm2, leading to increased p53 levels.
Arf
Increased p53 levels can lead to __ or __.
cell-cycle arrest or apoptosis
__, which involves the accumulation of proteins and other macromolecules, accompanies cell division.
Cell growth
Cell growth is the accumulation of proteins and other macromolecules by increasing the rate of __ and decreasing the rate of __ of proteins and macromolecules.
- synthesis
- degradation
Activates the kinase TOR, which stimulates metabolic processes in the cell.
phosphoinositide 3-kinase (PI 3-kinase)
What are two targets activated by TOR to stimulate protein synthesis?
- S6 kinase (S6K)
- eIF4E (translation initiation factor).
- In yeasts, the rate of cell division is governed by the rate of cell growth, with division occurring only when growth achieves a __.
- In yeast, what primarily regulates the rate of cell growth and division?
- minimal threshold
- Levels of extracellular nutrients
Programmed cell death, characterized by specific morphological changes and the formation of apoptotic bodies.
Apoptosis
Apoptotic bodies are removed and engulfed by __.
macrophages
Cell death in response to an acute insult, where cells swell, burst, and spill their contents, causing an inflammatory response.
Cell necrosis
A form of programmed cell death triggered by a specific regulatory signal from other cells.
Necroptosis
maintained by cells dying at the same rate as they are produced.
apoptosis
Tissue size
Sculpts hands and feet by causing the cells between spade-like structures to die, separating individual digits.
Cell death
During the transformation of a tadpole into a frog, the cells of the __ die through __ as the structure is no longer needed in the frog.
- tail
- apoptosis
In cell death, the __ process in development eliminates cells that are abnormal, misplaced, nonfunctional, or potentially dangerous to the animal.
quality-control
__ and __ must be tightly regulated to ensure that they are exactly in balance, maintaining proper tissue size and function.
- Cell death
- cell division
In this, cells may kill themselves by undergoing apoptosis to prevent further harm.
damages (DNA damage)
Apoptosis is triggered by specialized __ known as caspases.
intracellular proteases
have a cysteine at their active site and cleave target proteins at specific aspartic acids.
apoptosis
Caspases
begin the apoptotic process by forming dimers upon an apoptotic signal, leading to protease activation.
apoptosis
Initiator caspases
- are cleaved by initiator caspases to become active, leading to a proteolytic cascade that kills the cell.
- They amplify apoptosis through a proteolytic cascade that degrades cellular components, ensuring cell death.
apoptosis
Executioner caspases
Its cleavage leads to the irreversible breakdown of the nuclear lamina
Apoptosis
Lamin
Cleavage of __ frees the DNA-degrading endonuclease CAD, which cuts up the DNA in the cell nucleus.
apoptosis
iCAD
self-amplifying and irreversible
apoptosis
caspase cascade
What are the two pathways that trigger apoptosis? (2)
- extrinsic pathway
- intrinsic mitochondrial pathway
- are transmembrane proteins with an extracellular ligand-binding domain, a single transmembrane domain, and an intracellular death domain.
- belong to the TNF receptor family.
apoptosis
Death receptors
The ligands for death receptors are __, such as __ and __ ligand.
apoptosis
- homotrimers
- TNF
- Fas
Activation of Fas:
Binding of Fas ligand
→ __ domains on cytosolic tails bind __ proteins
→ __ proteins bind __
→ form the __(__)
→ activate __.
apoptosis
- death
- intracellular adaptor
- adaptor
- initiator caspases
- death-inducing signaling complex (DISC)
- executioner caspases
an inhibitory protein that helps prevent inappropriate activation of the extrinsic apoptosis pathway.
FLIP
It is triggered by stresses or developmental signals inside the cell, leading to the release of mitochondrial proteins into the cytosol.
apoptosis
intrinsic or mitochondrial pathway
After mitochondrial proteins are released into the cytosol, they activate a __ in the cytoplasm, leading to apoptosis.
caspase proteolytic cascade
released into the cytosol and binds to Apaf1 (apoptotic protease activating factor-1), leading to the formation of an apoptosome.
Cytochrome c
Cytochrome c is released into the cytosol and binds to __(__), leading to the formation of an apoptosome.
Apaf1 (apoptotic protease activating factor-1)
- a wheel-like heptamer formed by the oligomerization of Apaf1 after binding with cytochrome c.
- recruits initiator caspase-9 proteins, which activate the caspase cascade.
apoptpsome
The apoptosome recruits __, which activate the caspase cascade.
initiator caspase-9 proteins
a major class of intracellular regulators of the intrinsic apoptosis pathway, controlling the release of cytochrome c and other mitochondrial proteins into the cytosol.
Bcl2 family
What are the two types of Bcl2 family proteins? (2)
- Antiapoptotic
- pro-apoptotic proteins
Name two antiapoptotic Bcl2 family proteins. (2)
- Bcl2
- BclXL
What are the two categories of pro-apoptotic Bcl2 family proteins? (2)
- Effector Bcl2 family proteins
- Bh3-only proteins.
What triggers the activation of the intrinsic pathway of apoptosis?
apoptotic stimulus
After the intrinsic pathway is activated, what aggregate to form oligomers in the mitochondrial outer membrane, leading to the release of cytochrome c?
apoptosis
Bcl2 family proteins
Which proteins are the main effectors of the intrinsic pathway?
apoptosis
- Bax (in the cytosol)
- Bak (in the mitochondrial outer membrane)
They are located on the cytosolic surface of the outer mitochondrial membrane and prevent inappropriate release of intermembrane proteins by binding to and inhibiting pro-apoptotic Bcl2 family proteins.
anti-apoptotic proteins (like Bcl2 and BclXL)
- promote apoptosis mainly by inhibiting anti-apoptotic Bcl2 family proteins, enabling the aggregation of Bax and Bak on the mitochondria.
- triggers the instrincic pathway by enabling Bax and Bak aggregation on the mitochondrial surface, they trigger the release of intermembrane mitochondrial proteins that induce apoptosis.
BH3-only proteins
In response to DNA Damage, the tumor suppressor protein __ accumulates and activates the transcription of genes encoding __, such as __ and __, which trigger the intrinsic pathway.
- p53
- BH3-only proteins
- Puma
- Noxa
- proteins that prevent apoptosis by binding and inhibiting activated caspases; they were first identified in insect viruses.
- contain one or more __ domains, which enable them to bind and inhibit activated caspases.
inhibitors of apoptosis (IAPs)
- BIR (baculovirus IAP repeat)
- In Drosophila, this contain an IAP-binding domain that binds to the BIR domain of IAPs, preventing them from inhibiting caspases and promoting apoptosis.
- It is also released from the mitochondrial intermembrane space upon activation of the intrinsic pathway, blocking IAPs in the cytosol and promoting apoptosis.
Give 3 of this
Anti-IAPs
- Reaper
- Grim
- Hid
can inhibit apoptosis, promoting cell survival.
Extracellular signals
are produced in excess, and they compete for limited amounts of survival factors; those that receive enough survival signals live, while others die.
Nerve cells/Neurons
In the developing nervous system, the number of surviving neurons is automatically adjusted to be appropriate for the number of __ they connect with.
target cells
- What binds to cell-surface receptors, activating intracellular signaling pathways that suppress the apoptotic program?
- They regulate members of the __ family of proteins.
- They stimulate the synthesis of __ proteins.
- They inhibit the function of __ proteins such as Bad.
- They phosphorylate and inactivate __ like Hid, enabling IAP proteins to suppress apoptosis.
apoptosis
- survival factors
- Bcl2
- anti-apoptotic Bcl2
- pro-apoptotic BH3-only
- anti-IAP proteins
During cell death, Apoptotic cells and their fragments remain intact and are efficiently __ by neighboring cells.
phagocytosed
Chemical changes on the surface of the apoptotic cell recruit __ trigger the recruitment of phagocytic cells to apoptotic cells
phagocytic cells
normally resides in the inner leaflet of the lipid bilayer, flips to the outer leaflet in apoptotic cells, signaling for phagocytosis.
Phosphatidylserine
Healthy cells express __ that interact with __ on macrophages, blocking phagocytosis of healthy cells.
Macrophages distinguish between healthy and apoptotic cells
- signal proteins
- inhibitory receptors
Both __ and __ apoptosis can lead to various diseases, including cancer and autoimmune disorders.
- excessive
- insufficient
Cells die by necrosis as a result of ischemia during __ or __.
- heart attacks
- strokes
Inactivation of the genes encoding the __ or the __ can prevent normal lymphocyte death, leading to accumulation and autoimmune diseases.
- Fas death receptor
- Fas ligand
__ apoptosis in tumors allows cancer cells to regulate their apoptotic program abnormally, contributing to tumor growth.
Decreased
A chromosome translocation causing excessive production of the Bcl2 protein is associated with B cell lymphoma, inhibiting apoptosis.
Bcl2 gene
The regulation of apoptosis affects sensitivity to __ by inhibiting __, cancer cells can decrease their sensitivity to anticancer drugs, making treatment less effective.
- anticancer drugs
- apoptosis
What percentage of human cancers involve mutations in the gene encoding the tumor suppressor protein p53?
50%
Mutated __ can no longer promote apoptosis or cell-cycle arrest in response to DNA damage, allowing cancer cells to survive and proliferate despite DNA damage.
p53
drugs that are small chemicals that interfere with the function of __, promoting cell death.
anti-apoptotic Bcl2 family proteins
