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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
Q

___________ bind and inhibit CDK kinase activity (ex. Cip/Kip family: p21, p27, p57 - broad spectrum and INK4 family: p16 -inhibit cyclin D/Cdk4)

A

CKIs (Cyclin Kinase Inhibitors)

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26
Q

Inhibitory phosphorylations on cdk1 catalyzed by ________ kinase

A

Wee1

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27
Q

Inhibition of cdk1 is reversed by __________ phosphatase

A

Cdc25

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28
Q

Cyclin-Cdk is activated by Cdc25, which is a _______________

A

phosphatase

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29
Q

Cyclin-Cdl is inhibited by Wee1, which is a ______________

A

kinase

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30
Q

Decision at G1 to exit the cycle cycle and cells do not divide again

A

Terminal differentiation

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31
Q

Cells have a limited lifespan (telomere shortening)

Exit the cell cycle at G1

A

Senescence

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32
Q

The amount of _______ helps to determine whether a cell commits to another cycle or enters G0

A

CDK2

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33
Q

Serum growth factors (mitogens) - PDGF, EGF, IGF, etc. ________ cell cycle entry at G1 (extracellular factors)

A

promote

34
Q

TGF-beta, cell-cell contact __________ cell cycle entry at G1 (extracellular signals)

A

inhibits

35
Q

Transcriptional repressor (tumor suppressor) that associates with the TF E2F when active and inhibits E2F

A

Rb

36
Q

Phosphorylation of ______ by Cyclin E/Cdk2 inactivates it - can no longer associate with EF2 to prevent tc

A

Rb

37
Q

Mutation in the tumor suppressor gene Rb can lead to ________________

A

Retinoblastoma

38
Q

During S phase, Cyclin E and Cyclin A are unregulated. Cyclin E/Cdk2 and cyclin A/Cdk2 trigger invitation of DNA replication and ____________ duplication

A

centrosome

39
Q

Cyclin/CDKs ___________ replication initiation throughout S phase

A

trigger

40
Q

Cyclin/CDKs ___________ re-inititation of replication until after mitosis

A

inhibit

41
Q

ORC

A

origin of replication complex

42
Q

Pre-RC complex

A

primes replication origins

43
Q

During the assembly phase (G1), there is ______ CDK activity. Pre-RC assembly is allowed, but there is no Pre-RC activation

A

low

44
Q

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)

A

high

45
Q

Major microtubule organizing center

Must duplicate to direct the assembly of a bipolar spindle at mitosis

A

centrosome

46
Q

Centrosomes are duplicated during ______ phase

A

S

47
Q

Centrosome duplication is controlled by:

A

Cyclin/CDK oscillations

48
Q

In G2, cyclin A-cdk1/cdk2, cyclin B-Cdk1 increase, but kinase is inhibited by __________ dependent phosphorylation

A

Wee1

49
Q

In G2, Wee1 is winning so cyclin-cdk remains _____________, which gives a time day

A

inactive

50
Q

The _____ phase responds to intracellular signaling to check for DNA damage and to ensure that DNA replication is complete and centrosomes are duplicated

A

G2

51
Q

During mitosis, active cyclin B/Cdk1 kinase increases since _________ phosphatase removes inhibitory phosphorylation

A

Cdc25 phosphatase

52
Q

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.

A

mitosis

53
Q

Three different types of microtubules of the spindle:

A

Astral microtubules
Kinetochore microtubules
Interpolar microtubules

54
Q

Two proteins that organize mitotic chromosomes:

A

Condensins and cohesins

55
Q

___________ shorten chromosomes through loop extrusion during prophase

A

Condensins

56
Q

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)

A

cohesins

57
Q

The E3 ligase ________ promotes anaphase by getting ride of cyclins and cohesins

A

APC

58
Q

Two steps of cytokinesis:

A

Contractile ring formation and abscission

59
Q

Mitotic exit is a “reversal” of mitotic activation, so mitotic ________ (A and B) are destroyed by the APC

A

cyclins

60
Q

During cytokinesis, the _______ midzone helps to determine cleavage plane

A

spindle

61
Q

The ___________ ring (actin and myosin II) is important for cytokinesis

A

contractile ring

62
Q

Remnant of the spindle midzone

A

Midbody

63
Q

_____________ kinase helps to define the midzone

A

Aurora B

64
Q

Aurora B kinase is a part of the ________ pathway

A

“no-cut pathway”

65
Q

___________ can be used for imaging cell cycle progression (red is G1, green is G2)

A

FUCCI (fluorescent ubiquitin cell cycle indicator)

66
Q

Many ____________ cells have S phase and mitosis only (no gaps) for rapid division and building of tissues

A

embryonic

67
Q

Cell cycle that has S phase and G phase (no mitosis) for generation of polyploid cells (found in the heart, liver, placenta)

A

Endocycle

68
Q

Separate homologs, then sisters to generate haploid germ cells (altered cell cycle)

A

Meiosis

69
Q

Segregation mistakes during mitosis lead to _________, a Hallmark of cancer

A

aneuploidy

70
Q

Hard to replicate regions of the genome (incomplete replication can lead to DNA breakage / translocations, then aneuploidy/mutations, then cancer predisposition)

A

Fragile sites

71
Q

____________ that inhibit the cell cycle include sensors, transducers, and effectors

A

Checkpoints

72
Q

3 important factors in the DNA damage checkpoint

A

ATM, ATR, p53

73
Q

DNA damage can trigger kinases to activate p53, which is a TF for p21. p21 is a CKI that:

A

blocks cell cycle progression

74
Q

Kinases activated by DNA damage activate Wee1 and inhibit Cdc25, which:

A

prevent progression into mitosis

75
Q

A childhood disease associated with genome instability
(growth retardation and abnormal development, stem cell failure, 1000 fold risk of of cancer)
FANCD2 mutation

A

Fanconi Anemia

76
Q

Cells lacking FANCD2 show unaligned acentric fragments and ___________, which are damaging and dangerous for the cell

A

micronuclei

77
Q

Loss of _________ re-sensitizes papillar cells to irradiation

A

FANCD2

78
Q

___________ can facilitate survival and propagation of damaged, radio-resistant cells

A

Polyploidy

79
Q

The spindle/chromosome attachment checkpoint senses:

A

a lack of chromosome attachment/ tension

80
Q

_______ is a key player in kinetochore interactions in the spindle/chromosome attachment

A

Mad2

81
Q

Cdc20 acts with APC (anaphase promoting complex) to less to loss of _______ between sister chromosomes

A

cohesion

82
Q

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.

A

APC (anaphase promoting complex)

MCT Exam 3 (9 decks)

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