Module 7: The Cell Cycle Part 1 (Overview, Control System, S Phase, Mitosis) Flashcards
All living organisms products of repeated rounds of __ and __.
- cell growth and division
What is the cycle of duplication and division called?
cell cycle
What is the fundamental task of the cell cycle?
- Passing on genetic information to the next generation of cells.
- To duplicate DNA and then segregate it into two copies.
What are the key components associated with the cell cycle? (3)
- Cell-cycle control system
- Major stages of the cell cycle
- Extracellular signals.
What are the two main phases of the cell cycle? (2)
- S phase (DNA synthesis)
- M phase (mitosis and cytokinesis)
What are the sequential stages of mitosis? (4)
Prophase → Metaphase → Anaphase → Telophase
What are the gap phases in the cell cycle? (2)
- G1 phase (between M phase and S phase)
- G2 phase (between S phase and mitosis)
What is the sequence of cell cycle phases?
G1 → S → G2 → M
When does cell growth occur during the cell cycle?
when and except?
Throughout the cell cycle, except during mitosis.
They provide time for the cell to monitor internal and external environments to ensure conditions are suitable and preparations are complete before committing to S phase and mitosis.
Gap phases
A specialized resting state that cells can enter.
G0
resting phase
What is the critical decision point in the cell cycle where a cell commits to entering the next phase?
organism - point; give 2
- yeasts - Start point
- mammalian cells - restriction point
Is the basic organization of the cell cycle conserved across eukaryotic cells? Do they have similar machinery and control mechanisms to drive and regulate cell-cycle events?
Yes
Which model organisms are commonly used to study the cell cycle to identify and characterize the genes and proteins that govern the fundamental features of cell division? (2)
- Saccharomyces cerevisiae (budding yeast)
- Schizosaccharomyces pombe (fission yeast)
Which model organism is commonly used to study the cell cycle for the biochemical dissection of cell-cycle control mechanisms?
Xenopus laevis (frog)
Which model organism is commonly used to study the cell cycle that is useful for genetic analysis of mechanisms underlying control and coordination of cell growth and division in multicellular organisms?
Drosophila melanogaster (fruit fly)
How can you determine the cell cycle stage in living cells?
Observing living cells under a microscope
How can you estimate the cell-cycle stage in budding yeast under a microscope?
By the size of the bud.
What tools are used to stain cells for identifying cell cycle stages? (2)
- DNA-binding fluorescent dyes
- antibodies recognizing specific cell components
What marker is used to detect cells in the S phase?
Bromodeoxyuridine (BrdU)
What instrument is used to measure a cell’s DNA content for cycle stage identification?
Flow cytometer
the cell-cycle control system operate like a __ that triggers the events of the cell cycle in a set sequence.
timer
If the cell-cycle control system malfunctions, it delays progression to the __ to allow machinery repair and prevent premature cycle progression.
M phase
the cell-cycle control system improve accuracy and reliability through a connected series of __.
biochemical switches
characteristics of the cell-cycle control system (3)
- Binary (on/off) - irreversible
- robust and reliable - backup mechanisms
- highly adaptable
What are the three major regulatory transitions in the cell cycle? (3)
1) Start (restriction point)
2) G2/M transition
3) Metaphase-to-anaphase transition
A major regulatory transition in the cell cycle in late G1 that commits to cell-cycle entry and chromosome duplication.
Start (restriction point)
A major regulatory transition in the cell cycle that triggers early mitotic events for chromosome alignment in metaphase.
G2/M transition
A major regulatory transition in the cell cycle that stimulates sister chromatid separation, mitosis completion, and cytokinesis.
Metaphase-to-anaphase transition
What happens if the control system detects problems inside or outside the cell?
what is used and what does it do?
blocks progression through the regulatory transitions
They regulate cyclical changes in the phosphorylation of intracellular proteins that initiate or regulate the major events of the cell cycle.
cyclin-dependent kinases (Cdks)
How are Cdks controlled?
molecule
by cyclins
What are the four classes of cyclins? (4)
- G1/S-cyclin
- S-cyclin
- M-cyclin
- G1-cyclin
activate Cdks in late G1
G1/S-cyclin
Bind Cdks soon after progression through Start and help stimulate chromosome duplication.
S-cyclins
activate Cdks that stimulate entry to mitosis at the G2/M transition
M-cyclins
govern the activities of the G1/S-cyclins
G1-cyclins
Cells that have a single Cdk protein that binds to all classes of cyclins.
Yeast cells
How many Cdks do vertebrates have? (#) What do these vertebrate Cdks correspond to? (3)
- 4
Corresponds to: - Two for G1-cyclins
- One for G1/S- and S-cyclins
- One for S- and M-cyclins
Besides activating its Cdk partner, it directs the Cdk to specific target proteins.
cyclin protein
Phosphorylates a different set of substrate proteins.
cyclin–Cdk complex
- In the __ of cyclin, the active site in the Cdk protein is partly obscured by a protein loop.
- In the __ of cyclin, the loop moves away from the active site, resulting in partial activation of the Cdk enzyme.
- absence
- presence
obscure-conceal/hide
Causes the loop to move away from the active site, resulting in partial activation of the Cdk enzyme.
Cyclin binding
What results when a separate kinase, the Cdk-activating kinase (CAK), phosphorylates an amino acid near the entrance of the Cdk active site?
full activation
In full activation, a separate kinase, the __(__), phosphorylates an amino acid near the entrance of the Cdk active site.
Cdk-activating kinase (CAK)
Phosphorylation at a pair of amino acids in the roof of the kinase active site inhibits the __ activity.
cyclin–Cdk complex
It phosphorylates and inhibits the cyclin–Cdk complex.
Wee1 protein kinase
It dephosphorylates to activate or increase the activity of the cyclin–Cdk complex.
Cdc25 phosphatase
Proteins that inactivate cyclin-Cdk complexes.
Cdk inhibitor proteins (CKIs)
What triggers progression through the metaphase-to-anaphase transition to the final stages of cell division?
Protein destruction
It is a ubiquitin ligase that stimulates the proteolytic destruction of specific regulatory proteins by proteosomes.
anaphase-promoting complex or cyclosome (APC/C)
In early mitosis, what protects the protein linkages that hold sister-chromatid pairs together? When is this destroyed? (2)
- securin
- At metaphase
The destruction of these inactivates most Cdks in the cell; it causes dephosphorylation of proteins.
- S-cyclins
- M-cyclins
A ubiquitin ligase that ubiquitylates CKI proteins in late G1 and destroys G1/S-cyclins in early S phase.
ubiquilation:enzymatic post-translational modification
SCF/SCF ubiquitin ligase
SKP1, CUL1, F-box protein (SCF) complex
Changes in its association with an activating subunit—Cdc20 in mid-mitosis or Cdh1 from late mitosis through early G1.
anaphase-promoting complex or cyclosome (APC/C) activity
Substrate-binding subunits of SCF that remain constant during the cell cycle.
F-box proteins
The cell cycle operated in early animal embryos depends exclusively on __
what mechanism?
post-transcriptional mechanisms
How is the cell cycle regulated in more complex organisms?
through transcriptional control
Major cell cycle regulatory proteins:
Protein kinases and protein phosphatases that modify Cdks (3)
- Cdk-activating kinase (CAK)
- Wee1 kinase
- Cdc25 phosphatase
Major cell cycle regulatory proteins:
Cdk inhibitor proteins (4)
- Sic1 (budding yeast)
- p27 (mammals)
- p21 (mammals)
- p16 (mammals)
Major cell cycle regulatory proteins:
Ubiquitin ligases and their activators (2)
ubiquitin ligase - activator
- anaphase-promoting complex or cyclosome (APC/C) - Cdc20, Cdh1
- SCF
DNA duplication and reproduction of protein packaging surrounding each DNA region.
what phase?
S phase
Occur with extreme accuracy, ensuring every nucleotide in the genome is copied once.
DNA replication
Specific sequences where DNA replication begins.
origins of replication
- In DNA replication, it unwinds the double helix.
- They are activated, leading to DNA unwinding and initiation of DNA synthesis.
DNA helicase
The replication machinery moves outward from the origin at two replication forks.
what phase?
Elongation phase
DNA replication in late mitosis and early G1.
what phase?
Initiation phase
A structure assembled during late mitosis and early G1 that licenses replication origins.
initiation phase
prereplicative complex (preRC)?
Duplication of a chromosome is not simply a matter of replicating the DNA at its core but also requires the duplication of these __ and their proper assembly on the DNA.
chromatin proteins
production of chromatin proteins increases during __
what phase?
S phase
Differences between heterochromatin and euchromatin? (2)
Chromosomes’ two structurally and functionally diff. territories
- highly condensed
- more open
A pair of identical chromatids glued together along their length.
sister chromatids
What does sister-chromatid cohesion depend on? It holds sister chromatids together during metaphase.
cohesin
What do you call the two subunits of cohesin which forms giant ring-like structures?
SMC proteins
SMC-structural maintenance of chromosomes
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.
mitosis stage
Prophase
Starts abruptly with the breakdown of the nuclear envelope. Chromosomes attach to spindle microtubules via their kinetochores and undergo active movement.
mitotic stage
Prometaphase
The chromosomes align at the equator of the spindle, midway between the spindle poles. The kinetochore microtubules attach sister chromatids to opposite poles of the spindle.
mitotic stage
Metaphase
Sister chromatids synchronously separate to form two daughter chromosomes, which are pulled slowly toward the spindle poles they face. The kinetochore microtubules shorten, and the spindle poles move apart, contributing to chromosome segregation.
mitotic stage
Anaphase
The two sets of daughter chromosomes arrive at the spindle poles and decondense. A new nuclear envelope reassembles around each set, forming two nuclei and marking the end of mitosis. Cytoplasmic division begins with contraction of the contractile ring.
mitotic stage
Telophase
The cytoplasm is divided in two by a contractile ring of actin and myosin filaments, which pinches the cell in two to create two daughter cells, each with one nucleus.
mitotic stage
Cytokinesis
During mitosis, it induces the assembly of the mitotic spindle and ensures that each sister chromatid is attached to the opposite pole of the spindle.
M-Cdk
During mitosis, it triggers chromosome condensation and promotes the breakdown of the nuclear envelope during mitosis.
M-Cdk
M-Cdk facilitate the __ and rearrangements of the __ and the __.
- nuclear envelope breakdown
- actin cytoskeleton
- Golgi apparatus
How does M-Cdk function at the molecular level?
chemical reaction and to what?
By phosphorylating specific proteins.
It is required for the normal assembly of a bipolar mitotic spindle.
Polo-like kinase (Plk)
During mitosis, __ controls proteins that govern the assembly and stability of the spindle, while __ controls the attachment of sister chromatids to the spindle.
- Aurora kinases A
- Aurora kinases B
The accumulation of __ initiates the activation of M-Cdk.
M-cyclin
Which kinases contribute to the stockpile of M-Cdk? (2)
- Cdk-activating kinase (CAK)
- Wee1 (inhibitory protein kinase)
In M-Cdk activation, what activation removes the inhibitory phosphate that restrains M-Cdk?
activation of phosphatase Cdc25
What happens to the inhibitory activity of the kinase Wee1 during M-Cdk activation?
suppressed
During the activation of M-Cdk, it demonstrate positive feedback loops. It activates its own activator (__) and inhibits its own inhibitor (__).
- Cdc25
- Wee1
The purpose of reorganizing __ during prophase is to create relatively short, distinct structures that can be pulled apart more easily in anaphase.
sister chromatids
During __, chromatids are compacted.
chromosome condensation
The process by which two sister chromatids are resolved into distinct, separable units.
sister-chromatid resolution
Essential for sister-chromatid resolution; a five-subunit protein complex.
condensin
What are the components of the condensin complex? (2)
- 2 SMC subunits
- 3 non-SMC subunits.
The __ promote the compaction and resolution of sister chromatids by forming a ringlike structure that uses the energy provided by __.
- condensin complex
- ATP hydrolysis
What does chromosome segregation depend on?
mitotic spindle
What triggers the assembly of the mitotic spindle during mitosis?
M-Cdk
A bipolar array of microtubules.
mitotic spindle
Microtubules that overlap with the plus ends of microtubules from the other pole.
interpolar microtubules
Microtubules that are attached to sister-chromatid pairs at large protein structures called kinetochores.
kinetochore microtubules
Microtubules that radiate outward from the poles and contact the cell cortex.
astral microtubules
A cloud of pericentriolar matrix that surrounds a pair of centrioles.
centrosome
- Proteins are involved in the mitotic spindle’s function.
- coiled-coil proteins that link the motors to the centrosome, structural proteins, and components of the cell-cycle control system.
Microtubule-dependent motor proteins
What complexes are contained within the centrosome?
γ-tubulin ring complexes
Types of motor proteins are involved in spindle function:
Which moves toward the plus ends?
Which moves toward the minus ends?
- Kinesin-related proteins
- dyneins
They move toward the plus ends, sliding two antiparallel microtubules past each other toward the spindle poles, pushing the poles apart.
a kinesin-related protein
kinesin-5
They are minus-end directed motors that cross-link antiparallel interpolar microtubules at the spindle midzone and tend to pull the poles together.
a kinesin-related protein
kinesin-14
Plus-end directed motors that associate with chromosome arms and push the attached chromosome away from the pole.
a kinesin-related protein
Kinesin-4/10 or chromokinesins
They are minus-end directed motors that pull the spindle poles toward the cell cortex and away from each other.
dynein motor proteins
The mitotic spindle must have two poles to function properly.
Bipolarity of spindle
What does the bipolarity of the spindle depend on?
centrosome
The centrosome duplicates when the cell enters the __ of the cell cycle.
S phase
helps initiate centrosome duplication.
G1/S-Cdk
During __, the two centrioles in the centrosome separate, and each nucleates the formation of a single new centriole.
centrosome duplication
Structure surrounds the pairs of centrioles during duplication
enlarged pericentriolar matrix
What type of mechanism is used for centrosome duplication?
semiconservative mechanism
How often must the centrosome replicate in a cell cycle?
only once per cell cycle
When does spindle assembly begin during the cell cycle?
In early mitosis
Motor proteins that pull the spindle by linking astral microtubules to the cell cortex.
Dynein motor proteins
The __ ends of the microtubules between the centrosomes interdigitate to form interpolar microtubules.
interdigitate-interlock
plus
What factors promote centrosome separation and increase spindle length? (2)
- Dynein motors
- kinesin-5 motors
Which kinases phosphorylate kinesin-5 motors during spindle assembly? (2)
- M-Cdk
- Aurora-A
During mitosis, centrosomes and microtubules are located in the __, while chromosomes are located in the __.
- cytoplasm
- nucleus
During mitosis, the removal of the __ allows the attachment of sister-chromatid pairs to the spindle.
nuclear membrane
In __, M-Cdk phosphorylates several subunits of the nuclear pore complexes and components of the nuclear lamina during nuclear envelope breakdown.
nuclear envelope breakdown
During __, an abrupt change in the cell’s microtubules occurs, resulting in a larger number of shorter and more dynamic microtubules emanating from both centrosomes.
entry to mitosis
The __ of microtubules decreases during prophase, prometaphase, and metaphase.
half-life
In the spindle, it promotes stability and includes catastrophe factors that destabilize microtubule plus ends, contributing to the dynamic nature of spindle microtubules.
microtubule-associated proteins (MAPs)
In spindle formation, it creates a local environment that favors both microtubule nucleation and stabilization.
chromosomes
In spindle formation, it bounds to the chromatin activates Ran-GTP, which releases microtubule-stabilizing proteins, promoting nucleation and stabilization of microtubules around chromosomes.
guanine nucleotide exchange factor (GEF)
The ability of __ to stabilize and organize microtubules enables cells to form bipolar spindles in the absence of __.
- chromosomes
- centrosomes
Cells in __, __, and animal __ that develop from eggs without __ can form spindles without centrosomes.
- higher plants
- animal oocytes
- embryos
- fertilization
A giant, multilayered protein structure built at the centromeric region of the chromatid.
kinetochore
The __ ends of kinetochore microtubules are embedded head-on in specialized microtubule attachment sites at the kinetochore.
plus
a rod-shaped protein complex that links the microtubule to the kinetochore.
microtubule attachment
Ndc80
unstable lateral attachments, where the kinetochore attaches to the side of a passing microtubule.
kinetochore attachments
initial attachment
Dynamic microtubule plus ends capture the kinetochores in the correct __ orientation.
end-on
In the absence of __ during kinetochore attachment, microtubules near the chromosomes embed in the __-end-binding sites of the kinetochore, and polymerization at these plus ends drives the growth of microtubules away from the kinetochore.
- centrosomes
- plus
What do you call the form/orientation when sister chromatids in a pair attached to opposite poles of the mitotic spindle? What ensures proper tension and attachment stability?
- Bi-orientation
- Back-to-back orientation
During mitosis, this is corrected by a system of trial and error, as they are highly unstable and do not persist.
Incorrect attachments
The kinetochore senses correct attachments through __; __ (e.g., when both sister chromatids attach to the same spindle pole) triggers an inhibitory signal to loosen the attachment.
- tension
- low tension
- a protein kinase crucial for the tension-sensing mechanism during chromosome attachment
- generates an inhibitory signal that reduces the strength of microtubule attachment in the absence of tension.
- decrease the strength of microtubule attachment by phosphorylating some components at the microtubule attachment site, it decreases their affinity for the microtubule plus end.
Aurora-B
initiates sister-chromatid separation by ubiquitylating several mitotic regulatory proteins and thereby triggering their destruction
anaphase-promoting complex (APC/C)
- cohesins hold sister chromatids together
- loss of sister-chromatid cohesion
what mitotic stage? (2)
- metaphse
- anaphase
It targets securin, an inhibitory protein, for destruction, which activates separase to cleave cohesin subunits.
In the separation of sister chromatids
anaphase-promoting complex (APC/C)
In mitosis, securin inhibits the activity of __ until it is destroyed by APC/C.
separase
When APC/C targets __ and __ for destruction, Cdk inactivation occurs, allowing phosphatases to dephosphorylate Cdk targets, which is required for completing mitosis and cytokinesis.
- S-cyclin
- M-cyclin
It blocks progression through the metaphase-to-anaphase transition until all chromosomes are correctly bi-oriented on the mitotic spindle.
spindle assembly checkpoint
In spindle assembly checkpoint, an unattached kinetochore catalyzes a change in Mad2 conformation, enabling it to bind and inhibit __.
Cdc20-APC/C
binds to and inhibits Cdc20-APC/C, preventing the metaphase-to-anaphase transition if there are unattached kinetochores.
Mad2
What is triggered when there is a sudden loss of sister-chromatid cohesion at the onset of anaphase?
chromosome segregation
The initial poleward movement of chromosomes, driven by microtubule depolymerization at the kinetochore and microtubule flux.
mitotic stage
Anaphase A
The separation of spindle poles themselves.
mitotic stage
Anaphase B
- Disassembly of the mitotic spindle.
- Reformation of the nuclear envelope around the two sets of chromosomes.
- Packaging of chromosomes into daughter nuclei.
mitotic stage
Telophase
It promotes spindle assembly, chromosome condensation, and nuclear envelope breakdown.
M-Cdk phosphorylation
How is the mitotic spindle disassembled and daughter nuclei reformed?
a chemical reaction
dephosphorylation
dephosphorylation and the completion of mitosis is triggered by the inactivation of __, the activation of __, or both
- Cdks
- phosphatases
