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Flashcards covering the phases of the cell cycle, mitosis, sister chromatid separation, cyclins and CDKs, DNA damage responses, and cell-cycle checkpoints.
Which extracellular signal commonly encourages mammalian cells to enter the cell cycle?
Mitogenic growth factors
What is a typical early response to growth factor binding to its receptor?
Activation of intracellular growth-signaling cascades
Which pathway can transmit a mitogenic signal toward cell-cycle entry?
RAS-RAF-MEK-ERK
What does the restriction point in late G1 represent?
Commitment to cell-cycle progression when conditions permit
Which sequence correctly lists the major phases of the cell cycle?
G1, S, G2, M
What is the main purpose of G1 phase?
Cell growth and preparation for DNA replication
What occurs during S phase?
DNA replication
What is a major event during G2 phase?
Checking replicated DNA and preparing for mitosis
What is G0 phase in the cell cycle?
A quiescent state outside the active division cycle
Which events occur during M phase?
Nuclear division and usually cytokinesis
What occurs during prophase of mitosis?
Chromosomes condense and the spindle begins to assemble
Which events characterize prometaphase?
Nuclear envelope breakdown and kinetochore attachment
At which mitotic stage are chromosomes aligned at the metaphase plate?
Metaphase
Which cellular structure attaches spindle microtubules to chromosomes?
Kinetochore
What initiates anaphase during mitosis?
Activation of separase and cleavage of sister-chromatid cohesin
What protein holds sister chromatids together before anaphase?
Cohesin
What is the function of securin before anaphase?
Inhibits separase
Which protein complex promotes securin degradation at the metaphase-anaphase transition?
APC/C
What occurs during telophase?
Nuclear envelopes reform around separated chromosomes
What is cytokinesis?
Physical division of the cytoplasm into daughter cells
What is a cyclin-dependent kinase (CDK)?
A protein kinase whose activity is regulated by cyclins and other controls
What do cyclins primarily do in cell-cycle regulation?
Bind and help activate specific CDKs
Which property best describes CDK proteins during a typical cell cycle?
Their abundance is often more stable than that of their cyclin partners
Why do cyclin concentrations rise and fall during the cell cycle?
Regulated synthesis and proteolysis coordinate phase transitions
Which complex is associated with early G1 progression?
Cyclin D-CDK4/6
Which complex is strongly associated with the G1/S transition?
Cyclin E-CDK2
Which cyclin-CDK complex is a major driver of entry into mitosis?
Cyclin B-CDK1
What is a major effect of phosphorylation of RB protein during G1?
Release of E2F activity to promote S-phase gene expression
Which regulator can inhibit cyclin-CDK complexes after DNA damage?
p21
How does destruction of cyclin B contribute to mitotic exit?
Reduces CDK1 activity
Which enzyme family marks many cell-cycle regulators for proteasomal degradation?
Ubiquitin ligases
What factors determine CDK activity?
Cyclin binding, phosphorylation state, and inhibitory proteins
Which protein is a major transcriptional regulator of the DNA damage response?
p53
Which kinases play central roles in sensing or signaling DNA damage?
ATM and ATR
How can p53 promote G1 arrest?
By increasing p21 expression, which inhibits cyclin-CDK activity
What is a common cellular response to DNA damage that can be repaired?
Temporary cell-cycle arrest while repair occurs
What can happen when DNA damage is severe and cannot be repaired?
Apoptosis or cellular senescence
What is the likely consequence of losing effective DNA damage checkpoint control?
Greater genomic instability
What is the primary purpose of cell-cycle checkpoints?
Prevent progression when key events are incomplete or errors are detected
What does the G1/S checkpoint assess?
DNA integrity and conditions suitable for replication
Which checkpoint prevents entry into mitosis when DNA replication is incomplete?
G2/M checkpoint
What does the spindle assembly checkpoint monitor?
Proper chromosome attachment to the mitotic spindle
What happens if a kinetochore is not correctly attached to spindle microtubules?
Anaphase onset is delayed
Which consequence can result from checkpoint failure during mitosis?
Chromosome missegregation and aneuploidy
Which checkpoint is most directly involved in preventing replication of damaged DNA?
G1/S checkpoint
What is the major benefit of delaying the cell cycle after DNA damage?
Time for repair before DNA is replicated or segregated
If a cell has not completed DNA replication, which cell-cycle transition should be blocked?
G2 to M
If a chromosome is unattached at metaphase, which outcome is expected with a functional checkpoint?
APC/C activation is delayed
Which condition best permits progression past the G1/S checkpoint?
Adequate growth signaling and no unresolved major DNA damage
Which event follows successful satisfaction of the spindle assembly checkpoint?
APC/C activation enables anaphase onset
What substrate does separase cleave to allow sister chromatids to separate?
Sister-chromatid cohesin
Which inhibitor holds separase inactive prior to anaphase?
Securin
What protein complex targets securin for degradation at the metaphase-anaphase transition?
APC/C
What effect does increased p21 expression have on cyclin-CDK activity during G1 arrest?
It inhibits cyclin-CDK activity
Which transcription factor activity is released upon phosphorylation of the RB protein?
E2F activity
What type of gene expression is stimulated by released E2F activity during G1?
S-phase gene expression
Which CDK partner combines with cyclin B to drive mitotic entry?
CDK1
Which kinase partners are associated with cyclin D during early G1 progression?
CDK4 and CDK6
Which CDK partner combines with cyclin E at the G1/S transition?
CDK2
What mechanism acts alongside regulated synthesis to control cyclical fluctuations in cyclin concentration?
Proteolysis (proteasomal degradation)