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PRIVETTE-VINNEDGE 3 Flashcards

1
Q

What is the main purpose of the G2 phase?

A

The G2 phase ensures the DNA is replicated and undamaged before the cell enters mitosis.

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2
Q

How long does the G2 phase typically last?

A

The G2 phase is relatively short, taking only about 4 hours to complete.

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3
Q

What happens if DNA damage, particularly double-strand breaks, is detected during G2?

A

Homologous recombination DNA repair is activated, using the sister chromatid created during S phase as a template.

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4
Q

Which kinases are involved in mediating homologous recombination repair?

A

ATM/ATR kinases mediate HR repair.

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5
Q

What is the consequence of checkpoint activation in response to DNA damage?

A

Checkpoint activation inhibits the M phase cyclin-CDK complex (Cyclin B/CDK1), preventing entry into mitosis until the damage is repaired.

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6
Q

What triggers the transition from G2 to M phase?

A

An inactive DNA damage checkpoint signals that the DNA is intact and replication is complete, allowing the cell to proceed to mitosis.

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7
Q

Besides DNA repair, what other important processes occur during the G2 phase?

A

The cell accumulates essential proteins required for mitosis, including mitotic checkpoint proteins, mitotic spindle proteins (tubulins), and cytokinesis proteins.

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8
Q

What are centrosomes composed of?

A

Each centrosome consists of two centrioles.

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9
Q

When are centrosomes duplicated?

A

Centrosomes are duplicated during the S phase, initiated by cyclin E/CDK2.

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10
Q

When do centrosomes elongate and mature?

A

Centrosomes elongate and mature during the G2 phase.

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11
Q

What happens to the centrosomes during the M phase?

A

The duplicated centrosomes are separated and move to opposite poles of the cell during the M phase.

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12
Q

What is the master regulator of centrosome duplication?

A

PLK4 kinase plays a crucial role in regulating centrosome duplication.

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13
Q

What is another name for centrosomes?

A

Centrosomes are also known as microtubule-organizing centers (MTOCs).

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14
Q

What is the primary function of centrosomes?

A

Centrosomes serve as the origin for microtubule nucleation and mitotic spindle pole formation.

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15
Q

What protein serves as a marker for centrosomes?

A

Gamma (γ) tubulin is a specific marker for centrosomes.

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16
Q

Which kinases are essential for centrosome maturation, separation, and movement to opposite poles of the cell?

A

Aurora kinase and Polo-like kinase 1 (PLK1) are critical for these centrosome-related processes.

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17
Q

How do centrosomes move towards the poles of the cell?

A

They recruit KIF11, a microtubule-dependent motor kinesin-like protein, which pushes them towards the poles.

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18
Q

What are the two main mitotic checkpoints?

A

The two main mitotic checkpoints are the Antephase (Prophase) Checkpoint and the Metaphase Checkpoint.

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19
Q

What does the Antephase (Prophase) Checkpoint monitor?

A

It checks if the mitotic spindle can develop properly by assessing microtubule polymerization and stability during prophase.

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20
Q

How is the activation of the Antephase Checkpoint assessed?

A

It’s assessed by comparing the percentage of cells in prophase versus other cell cycle stages.

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21
Q

What is the primary focus of the Metaphase Checkpoint?

A

This checkpoint determines if all sister chromatids are attached to the mitotic spindle and correctly aligned at the metaphase plate.

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22
Q

What molecular complex drives the Metaphase Checkpoint?

A

The mitotic checkpoint complex (MCC), composed of BubR1, Bub3, Mad2, and Cdc20, is responsible for this checkpoint.

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23
Q

How does the MCC exert its control at the Metaphase Checkpoint?

A

The MCC inhibits the Anaphase Promoting Complex (APC/C), preventing the separation of sister chromatids until proper attachment is ensured.

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24
Q

What holds sister chromatids together until the Metaphase Checkpoint is satisfied?

A

The Cohesin complex maintains the connection between sister chromatids.

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25
What factors can activate the Prophase/Antephase checkpoint?
This checkpoint can be triggered by cold temperatures and microtubule-targeting drugs like paclitaxel and nocodazole.
26
What is the key mediator of the Prophase/Antephase checkpoint?
CHFR, an E3 ubiquitin ligase, plays a crucial role in this checkpoint.
27
What is the full name of CHFR?
CHFR stands for Checkpoint with Forkhead-associated and RING finger domains.
28
How does microtubule instability affect CHFR?
Microtubule instability leads to the stabilization of CHFR.
29
What is the function of CHFR in the checkpoint?
CHFR ubiquitinates PLK1, targeting it for degradation. This allows Wee1 kinase to inhibit CDK1, halting the cell cycle.
30
What other kinase can activate this checkpoint pathway?
p38 MAPK kinase, a stress sensor, can also activate the Prophase/Antephase checkpoint pathway.
31
Where are checkpoint proteins located during metaphase?
They are localized to the kinetochore.
32
What is the kinetochore?
It is the centromere region of the chromosome where the spindle microtubules attach.
33
What is the role of CENP-E in metaphase?
CENP-E, a centromeric kinesin motor protein, binds to unattached kinetochores and pulls them towards the microtubule spindles.
34
What happens when CENP-E binds to microtubules?
CENP-E releases Aurora kinases, which triggers the transition into anaphase.
35
What activates the metaphase checkpoint?
The checkpoint is activated by the absence of tubulins or tension at the kinetochore, indicating improper attachment of chromosomes to the spindle.
36
What happens to CENP-E when it is not attached to microtubules?
It restricts Aurora kinases and activates BUB1.
37
What are the roles of BUB1 and MPS1?
Both BUB1 and MPS1 are kinases.
38
How does MAD2 function in the metaphase checkpoint?
MAD2 undergoes a conformational change upon kinetochore attachment to spindle tubulins, contributing to checkpoint signaling.
39
What is the consequence of activating the metaphase checkpoint?
Activation of this checkpoint blocks the Anaphase Promoting Complex (APC/C), preventing the cell from progressing to anaphase.
40
What is a common consequence of the loss of mitotic checkpoints?
Loss of mitotic checkpoints frequently occurs in cancer.
41
Why are CHFR and other checkpoint proteins considered tumor suppressors?
They prevent uncontrolled cell division by ensuring proper chromosome segregation. Defects in these proteins can contribute to tumor development.
42
What happens when mitotic checkpoints are defective?
Mitosis can occur even if the mitotic spindle and sister chromatids are not properly connected, leading to errors in chromosome segregation.
43
What is the result of improper chromosome segregation into daughter cells?
It results in chromosome instability (CIN), leading to aneuploidy.
44
How can chromosome instability (CIN) be detected?
CIN can be detected by observing lagging or misaligned chromosomes, micronuclei by immunofluorescence, and DNA content greater than 4N by flow cytometry.
45
What is aneuploidy?
Aneuploidy refers to having an abnormal number of chromosomes in a cell.
46
What problems can arise from having more centrosomes than normal?
Excessive centrosomes can lead to the formation of multipolar spindles, contributing to chromosome missegregation and aneuploidy.
47
Describe the state of chromatin during interphase.
Interphase chromatin is already compacted but requires further condensation during mitosis.
48
What mediates chromatin condensation during mitosis?
Condensation is mediated by Condensin I and II complexes and histone modifications.
49
How is chromosome looping accomplished during condensation?
Condensins facilitate chromosome looping through a loop exclusion process.
50
What defines the boundaries of chromosome loops?
CTCF protein binding sites mark the boundaries of chromosome loops.
51
What type of motor protein is believed to be involved in chromatin condensation?
Evidence suggests that a chromatin kinesin motor protein, possibly KIF4, is required for this process.
52
What are topologically associating domains (TADs)?
TADs are folded chromatin loops that span hundreds of kilobases, contributing to the three-dimensional organization of the genome.
53
What techniques can be used to identify the long-range cis-interactions that form TAD structures?
Techniques based on proximity-ligation and sequencing, such as Hi-C, can be used to map these interactions genome-wide.
54
What are the two main processes involved in chromatin condensation?
Condensation involves loop formation by condensins and histone H3 and H4 modifications.
55
How does PLK1 contribute to histone modifications during condensation?
PLK1 activates Haspin, which phosphorylates histone H3 at threonine 3 (T3).
56
What is the role of Aurora B kinase in histone modifications?
Aurora B kinase phosphorylates histone H3 at serine 10 (S10) and serine 28 (S28).
57
What is the line in the middle of metaphase called?
The metaphase plate
58
The midbody is based on _______ and ________.
actin, septins
59
The ______ spindles of the microtubules point away from the cell.
astral
60
__________ microtubules are microtubules that connect to each other and act as the pulling force.
Interpolar
61
What happens to histone H4 during condensation?
Histone H4 undergoes deacetylation at lysine 16 (K16) by Hst2p.
62
The Antephase (Prophase) Checkpoint is for the _______, while the Metaphase Checkpoint was discovered first and is for checking that the spindles are attached to every ________.
microtubules, sister chromatid
63
How is histone H3 methylation reversed after mitosis?
PP1 phosphatase reverses histone H3 methylation.
64
What is cytokinesis?
Cytokinesis is the final stage of the cell cycle, where a single cell divides into two daughter cells.
65
True or False: Extra centrosomes are always bad and will cause errors.
True, conserved across species and cell types
66
What events occur during telophase and cytokinesis?
The nuclear envelope reassembles, and a contractile ring forms, leading to the division of the cytoplasm.
67
What forms the contractile ring during cytokinesis?
The contractile ring is made of actin filaments and myosin.
68
What is the cleavage furrow?
The cleavage furrow is the indentation that forms in the cell membrane as the contractile ring pinches the cytoplasm.
69
What is abscission?
Abscission is the final separation of the two daughter cells.
70
What is the role of PRC1 in cytokinesis?
PRC1 (Protein Regulation of Cytokinesis 1), a microtubule-associated protein, helps regulate the process of cytokinesis.
71
What is the function of the Chromosomal Passenger Complex (CPC)?
The CPC plays a key role in controlling chromosome segregation and cytokinesis.
72
How does Rho-associated Kinase (ROCK) contribute to cytokinesis?
ROCK is involved in regulating the assembly and contraction of the contractile ring.
73
What is the role of ECT2 in cytokinesis?
ECT2 is a Rho-GEF that activates Rho GTPases, which are essential for contractile ring formation.
74
What is the function of the Central Spindle Complex (CSC2/Borealin)?
The Central Spindle Complex helps organize the microtubules in the central spindle, which is crucial for cytokinesis.
75
What is the function of Myosin II motor proteins during cytokinesis?
Myosin II motor proteins drive the contraction of the central ring at the cleavage furrow, leading to cell separation.
76
What is the role of the Endosomal Sorting Complex Required for Transport (ESCRT) in cytokinesis?
The ESCRT complex is part of the abscission machinery, responsible for the final cutting of the membrane connection between daughter cells.
77
What are septins (SEPT)?
Septins are cytoskeletal scaffolding proteins that play important roles in cytokinesis.
78
How do septins contribute to cytokinesis?
They interact with anillin and myosin, facilitating the shrinkage of the cleavage furrow into the midbody.
79
What is the midbody?
The midbody is a transient structure that forms between the two daughter cells during cytokinesis, containing remnants of the spindle microtubules and other proteins.
80
How do septins facilitate abscission?
They help activate the ESCRT complex, which is required for the final membrane separation.
81
What other role do some septin proteins have in cell division?
Some septins bind to the kinetochore and facilitate chromosome alignment at the metaphase plate.
82
How do septins help develop the cytokinetic bridge/midbody?
They stabilize the structure of the cytokinetic bridge.
83
What structure do anillin and septins create during cytokinesis?
They form a "collar" that flanks the midbody.
84
What is the purpose of the "collar" formed by anillin and septins?
It helps recruit and localize the ESCRT-III complex, which is essential for abscission.
85
What can result from incorrect cytokinesis or multipolar spindles?
Errors in cytokinesis can lead to the formation of binucleated cells, which are single large cells with two or more nuclei.
86
What typically happens to normal binucleated cells?
Most normal binucleated cells either get stuck in the next G1 phase or undergo apoptosis.
87
In what type of cells are multinucleated cells considered normal?
Normal multinucleated cells are rare but are primarily observed in cardiomyocytes, the muscle cells of the heart.
88
Why are binucleated cells commonly seen in cancer?
Cancer-associated mutations can enable binucleated cells to continue proliferating.
89
What are the consequences of binucleated cells continuing to proliferate in cancer?
This can be a significant driver of aneuploidy and mutagenesis, contributing to tumor development and progression.
90
Why is the cell cycle a target for cancer therapy?
Cancer cells often exhibit uncontrolled cell cycle progression. Targeting cell cycle checkpoints and processes can inhibit their proliferation.
91
What types of drugs target the cell cycle in cancer treatment?
Examples include microtubule-targeting drugs (e.g., taxanes), CDK inhibitors, and DNA damaging agents.
92
What are the four main phases of the cell cycle?
The cell cycle consists of G1, S, G2, and M phases.
93
What is the role of cyclins and CDKs in the cell cycle?
Cyclins and cyclin-dependent kinases (CDKs) are regulatory proteins that control the progression through the cell cycle.
94
What are cell cycle checkpoints?
Checkpoints are control mechanisms that ensure the proper order and completion of cell cycle events and prevent errors in DNA replication and chromosome segregation.
95
What is the significance of chromosome instability (CIN) in cancer?
CIN is a hallmark of cancer and contributes to tumor heterogeneity, drug resistance, and metastasis.
96
What are some consequences of errors in mitosis?
Errors in mitosis can lead to aneuploidy, chromosome rearrangements, and cell death.
97
How does the cell cycle relate to tissue development and repair?
The cell cycle is essential for cell proliferation, which is crucial for tissue growth, development, and repair.
98
What is the role of apoptosis in maintaining tissue homeostasis?
Apoptosis, or programmed cell death, eliminates damaged or unwanted cells, preventing the accumulation of mutations and maintaining tissue health.
99
What is the difference between mitosis and meiosis?
Mitosis produces two identical daughter cells, while meiosis produces four genetically diverse daughter cells involved in sexual reproduction.
100
How does the cell cycle contribute to aging?
With each cell division, telomeres shorten, eventually leading to cellular senescence and contributing to the aging process.
101
True or False: The G2 phase is longer than the S phase.
False. The G2 phase is typically shorter than the S phase.
102
True or False: Centrosomes are only present during mitosis.
False. Centrosomes are present throughout the cell cycle but play a critical role in organizing the mitotic spindle during mitosis.
103
True or False: Activation of mitotic checkpoints promotes cell cycle progression.
False. Checkpoint activation halts or delays the cell cycle until specific conditions are met, ensuring the fidelity of cell division.
104
True or False: Cytokinesis occurs before mitosis.
False. Cytokinesis is the final stage of the cell cycle, following mitosis.
105
True or False: Errors in the cell cycle can contribute to the development of cancer.
True. Uncontrolled cell division and errors in DNA replication or chromosome segregation can lead to the accumulation of mutations and the development of cancer.

MolCell Mega Class (21 decks)

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