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MCT Exam 3 > Cell Cycle > Flashcards

Cell Cycle Flashcards

1
Q

Failure in regulation of cell cycle rate or pathways that control genome stability can lead to ________

A

cancer

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2
Q

Normal promote cycling through the cell cycle

Gain of function (dominant) mutations promote cancer

A

Proto-oncogenes

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3
Q

Normally restrain cycling through the cell cycle

Loss of function (recessive) mutants lead to tumor formation

A

Tumor suppressor genes

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4
Q

Examples of genome ____________ in cancer:
Whole chromosome aneuploidy
Translocations
Increased mutation rate

A

instability

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5
Q

What is yeast an ideal model organism for cell cycle systems?

A 
Fast
One cell 
Easily distinguishable phases 
Genetic screens 
Drug arrest
Highly conserved
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6
Q

Stage of the cell cycle that makes the commitment to divide and is initiated by extracellular signaling. Decision making stage (don’t want to waste energy dividing if you don’t really need to).

A

Gap 1 (G1)

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7
Q

Stage of the cell cycle that makes the commitment to mitosis and is initiated by intracellular signaling. Decision making stage to ensure everything went ok during duplication. (introspection)

A

Gap 2 (G2)

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8
Q

What are the key players in control of the cell cycle?

A

Cyclin-dependent kinase complex (cyclins, cdks)

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9
Q

catalytic subunit of the cyclin-dependent kinase complex

A

CDK

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10
Q

Component of the cyclin-dependent kinase complex that is responsible for activation and substrate specificity

A

Cyclin

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11
Q

Different proteins are targeted depending on which _________ binds to which CDK

A

cyclin

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12
Q

The cyclin-depdent kinase complex acts as a ______________ that promotes cell cycle progression by phosphorylating target proteins

A

molecular switch

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13
Q

Cyclin-CDK for G1

A

Cyclin D

Cdk4, Cdk6

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14
Q

Cyclin-CDK for G1/S

A

Cyclin E

Cdk2

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15
Q

Cyclin-CDK for S

A

Cyclin A

Cdk2, Cdk1

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16
Q

Cyclin-CDK for M

A

Cyclin B

Cdk1

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17
Q

Cdk expression remains consistent, but cyclin levels ___________, leading to oscillations in CDK activity (cyclin is key regulatory input)

A

oscillate

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18
Q

Two key features of cyclin-CDK regulation (to regulate and to keep it from reaching steady state)

A
  1. Negative feedback loop

2. A time delay in the negative feedback

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19
Q

Three ways the key players (cyclin/CDKs) are regulated as the cell cycle moves from one phase to the next

A
  1. Gene Transcription
  2. Cyclin Degradation
  3. Controlling CDK activity
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20
Q

Two mechanisms for how gene transcription is regulated during the cell cycle

A
  1. Cyclin/CDKs regulate some aspects of the cell cycle transcription network
  2. Sequential activation of transcription by CDK-indepndent TFs
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21
Q

What process regulates cyclin destruction?

A

Ubiquitin and proteasome-dependent proteolysis

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22
Q

______ ligases are specific to target specific proteins (like for the different cyclins) for ubiquitination

A

E3 ligases

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23
Q

Why does cyclin destruction need to occur and be regulated?

A

Need oscillations to keep cell cycle going, if not - the cycle locks and stops progressing

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24
Q

Three mechanisms for regulating CDK kinase activity

A
  1. Cyclin binding
  2. Inhibitor binding
  3. Phosphorylation
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25
___________ bind and inhibit CDK kinase activity (ex. Cip/Kip family: p21, p27, p57 - broad spectrum and INK4 family: p16 -inhibit cyclin D/Cdk4)
CKIs (Cyclin Kinase Inhibitors)
26
Inhibitory phosphorylations on cdk1 catalyzed by ________ kinase
Wee1
27
Inhibition of cdk1 is reversed by __________ phosphatase
Cdc25
28
Cyclin-Cdk is activated by Cdc25, which is a _______________
phosphatase
29
Cyclin-Cdl is inhibited by Wee1, which is a ______________
kinase
30
Decision at G1 to exit the cycle cycle and cells do not divide again
Terminal differentiation
31
Cells have a limited lifespan (telomere shortening) | Exit the cell cycle at G1
Senescence
32
The amount of _______ helps to determine whether a cell commits to another cycle or enters G0
CDK2
33
Serum growth factors (mitogens) - PDGF, EGF, IGF, etc. ________ cell cycle entry at G1 (extracellular factors)
promote
34
TGF-beta, cell-cell contact __________ cell cycle entry at G1 (extracellular signals)
inhibits
35
Transcriptional repressor (tumor suppressor) that associates with the TF E2F when active and inhibits E2F
Rb
36
Phosphorylation of ______ by Cyclin E/Cdk2 inactivates it - can no longer associate with EF2 to prevent tc
Rb
37
Mutation in the tumor suppressor gene Rb can lead to ________________
Retinoblastoma
38
During S phase, Cyclin E and Cyclin A are unregulated. Cyclin E/Cdk2 and cyclin A/Cdk2 trigger invitation of DNA replication and ____________ duplication
centrosome
39
Cyclin/CDKs ___________ replication initiation throughout S phase
trigger
40
Cyclin/CDKs ___________ re-inititation of replication until after mitosis
inhibit
41
ORC
origin of replication complex
42
Pre-RC complex
primes replication origins
43
During the assembly phase (G1), there is ______ CDK activity. Pre-RC assembly is allowed, but there is no Pre-RC activation
low
44
During the activation phase (S, G2, M), there is ______ CDK activity. Existing Pre-RCs are activated, and Pre-RC assembly is inhibited. (Promotes firing of origin, inhibits components of Pre-RC)
high
45
Major microtubule organizing center | Must duplicate to direct the assembly of a bipolar spindle at mitosis
centrosome
46
Centrosomes are duplicated during ______ phase
S
47
Centrosome duplication is controlled by:
Cyclin/CDK oscillations
48
In G2, cyclin A-cdk1/cdk2, cyclin B-Cdk1 increase, but kinase is inhibited by __________ dependent phosphorylation
Wee1
49
In G2, Wee1 is winning so cyclin-cdk remains _____________, which gives a time day
inactive
50
The _____ phase responds to intracellular signaling to check for DNA damage and to ensure that DNA replication is complete and centrosomes are duplicated
G2
51
During mitosis, active cyclin B/Cdk1 kinase increases since _________ phosphatase removes inhibitory phosphorylation
Cdc25 phosphatase
52
During __________, there is a breakdown of nuclear membrane and condensation of replicated chromosomes. Chromosomes must correctly attach to spindle, then and only then, chromosomes are allows to segregate.
mitosis
53
Three different types of microtubules of the spindle:
Astral microtubules Kinetochore microtubules Interpolar microtubules
54
Two proteins that organize mitotic chromosomes:
Condensins and cohesins
55
___________ shorten chromosomes through loop extrusion during prophase
Condensins
56
During the metaphase-anaphase transition, there is the timely destruction of ___________ to exit from mitosis that is medicated by APC-dependent proteolysis (an E3 ligase)
cohesins
57
The E3 ligase ________ promotes anaphase by getting ride of cyclins and cohesins
APC
58
Two steps of cytokinesis:
Contractile ring formation and abscission
59
Mitotic exit is a "reversal" of mitotic activation, so mitotic ________ (A and B) are destroyed by the APC
cyclins
60
During cytokinesis, the _______ midzone helps to determine cleavage plane
spindle
61
The ___________ ring (actin and myosin II) is important for cytokinesis
contractile ring
62
Remnant of the spindle midzone
Midbody
63
_____________ kinase helps to define the midzone
Aurora B
64
Aurora B kinase is a part of the ________ pathway
"no-cut pathway"
65
___________ can be used for imaging cell cycle progression (red is G1, green is G2)
FUCCI (fluorescent ubiquitin cell cycle indicator)
66
Many ____________ cells have S phase and mitosis only (no gaps) for rapid division and building of tissues
embryonic
67
Cell cycle that has S phase and G phase (no mitosis) for generation of polyploid cells (found in the heart, liver, placenta)
Endocycle
68
Separate homologs, then sisters to generate haploid germ cells (altered cell cycle)
Meiosis
69
Segregation mistakes during mitosis lead to _________, a Hallmark of cancer
aneuploidy
70
Hard to replicate regions of the genome (incomplete replication can lead to DNA breakage / translocations, then aneuploidy/mutations, then cancer predisposition)
Fragile sites
71
____________ that inhibit the cell cycle include sensors, transducers, and effectors
Checkpoints
72
3 important factors in the DNA damage checkpoint
ATM, ATR, p53
73
DNA damage can trigger kinases to activate p53, which is a TF for p21. p21 is a CKI that:
blocks cell cycle progression
74
Kinases activated by DNA damage activate Wee1 and inhibit Cdc25, which:
prevent progression into mitosis
75
A childhood disease associated with genome instability (growth retardation and abnormal development, stem cell failure, 1000 fold risk of of cancer) FANCD2 mutation
Fanconi Anemia
76
Cells lacking FANCD2 show unaligned acentric fragments and ___________, which are damaging and dangerous for the cell
micronuclei
77
Loss of _________ re-sensitizes papillar cells to irradiation
FANCD2
78
___________ can facilitate survival and propagation of damaged, radio-resistant cells
Polyploidy
79
The spindle/chromosome attachment checkpoint senses:
a lack of chromosome attachment/ tension
80
_______ is a key player in kinetochore interactions in the spindle/chromosome attachment
Mad2
81
Cdc20 acts with APC (anaphase promoting complex) to less to loss of _______ between sister chromosomes
cohesion
82
If the spindle/chromosome attachment checkpoint senses a problem with tension, Cdc20 is inhibited, which prevents association with _______. Therefore, the chromosomes will not pull apart.
APC (anaphase promoting complex)

MCT Exam 3 (9 decks)

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