Exam #4 Cell Cycle Flashcards

1
Q

Four Stages of the Cell Cycle

A
  • M= Mitosis, when the cell dividies
  • G1= Growth period the precedes DNA synthesis
  • S= DNA synthesis/replication to form two sister chromatids attached at centromere
  • G2= Second period of growth the precedes cell division
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2
Q

Stages of the Cell Cycle that Comprise Interphase

A

Interphase is the time between cell divisions

  • G1
  • S
  • G2
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3
Q

Cyclin-CDK Complexes of M-Phase

A
  • Cyclin A/CDK1

- Cyclin B/CDK1

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4
Q

Cyclin-CDK Complexes of Mid G1 Phase

A
  • Cyclin D/CDK 4

- Cyclin D/CDK6

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5
Q

Cyclin-CDK Complexes of Late G1 Phase

A

Cyclin E/CDK2

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6
Q

Cyclin-CDK Complexes of S Phase

A

Cyclin A/CDK2

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7
Q

Contact Inhibition

A
  • Cell - Cell contact usually inhibits cell division
  • This “contact inhibition” is lost in cancer
  • Cell - ECM contact does the opposite
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8
Q

Growth Factors

A
  • Molecules that stimulate cell growth/division

- PDGF, EGF, nerve growth factor, and insulin-like growth factor 1 are examples

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9
Q

Growth Factor Receptors

A
  • Intrinsic Tyrosine Kinase
  • Ligand (growth factor) binds to receptor & triggers receptor dimerization & autophosphorylation or tyrosine residues within the receptor
  • Phosphotyrosine residues are docking sites for signaling molecules
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10
Q

GRB2, Sos, & Ras

A
  • GRB2= adapter protein that binds phosphotyrosine residues
  • Sos= Guanine Nucleotide Exchange Factor, activates Ras
  • Ras= G-Protein that is activated by SOS
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11
Q

Raf, MAP kinase kinase, MAP kinase

A
  • Ras activates the protein kinase Raf
  • Raf phosphorylates & activates MAP Kinase Kinase (MEK)
  • MAP Kinase Kinase phosphorylates & activates MAP Kinase
  • MAP Kinase translocated to the nucleus and stimulates c-Fos transcription
  • End result= progression through the restriction point
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12
Q

Early Response Genes

A
  • Growth factor added to cell in G0 results in a burst of transcription
  • Genes transcribed in this initial phase are “early response genes”
  • Includes c-Fos, c-Jun, and c-Myc
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13
Q

Delayed Response Genes

A
  • Genes transcribed in response to c-Fos

- Encode more transcription factors & Mid/Late G1 Clycin-CDKs

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14
Q

Why is phosphorylation of Rb important?

A

It stimulates progression through the restriction point and renders the cell cycle growth factor independent

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15
Q

What kinases phosphorylate Rb?

A
  • CDK 4 & CDK 6 (Cyclin D regulated) initially

- CDK 2 (Cyclin E regulated) secondarily

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16
Q

How is cyclin A-CDK2 inhibited?

A

p27-KIP1

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17
Q

What does cyclin A-CDK2 inhibition prevent?

A

DNA Replication

18
Q

How is cyclin A-CDK2 inhibition relieved?

A

Cyclin E/CDK 2 (late G1) phosphorylation of p27-KIP1

19
Q

How is entry into mitosis coupled to completion of DNA replication?

A
  • Cyclin A & B/CDK1 are required for entry into mitosis
  • Both phosphorylated and inactive until replication is complete
  • Once replication is completed, Phosphatase Cdc25C removes inhibitory phosphate
20
Q

Why would normal cells not divide if chromosomes were not correctly attached to the mitotic spindle?

A
  • Anaphase is delayed until chromosomes attach to the spindle
  • Attachment activates the anaphase promoting complex (APC)
  • APC allows ubiquitination of cohesin that holds sister chromatids together at the centromere
  • Sister chromatids then move apart
21
Q

ATM

A
  • Senses replication forks i.e. ongoing replication
  • ATM prevents dephosphorylation & activation of Cyclin A/B- CDK1
  • ATM is active as long as replication forks are present; thus entry into M-phase is dependent on completion of replication
22
Q

Checkpoint Kinase

A
  • ATM activated

- Blocks the action of Phosphatase Cdc25C i.e. blocks activation of Cyclin A/B-CDK1 when replication is ongoing

23
Q

p53

A
  • Normally unstable transcription factor
  • Stabilized by ATM/ATR of DNA damage checkpoint
  • Upregulates p21-CIP1
24
Q

p21-CIP1

A
  • Inhibitor of Cyclin/CDK 1 & 2

- Blocks entry into S & M phase

25
Q

Define Apoptosis

A

programmed cell death

26
Q

Outline Apoptosis

A

1) Chromosome & Cytoplasmic condensation
2) Nuclear Fragmentation
3) Cell Fragmentation & Blebbing
4) Apoptotic Bodies formed
5) Phagocytosis

27
Q

Caspases

A
  • Caspase 9= Initiator Caspase

- Caspase 3= Executioner Caspase

28
Q

How does p53 activation lead to an efflux of cytochrome c from the mitochondria?

A
  • One of the targets of p53 is the Bcl-2 family of proteins, including PUMA, BID, & BAX
  • BAX activation forms a channel in the mitochondira
  • Cytochrome C comes out
29
Q

G0

A

Cells that have differentiated and are no longer dividing exit the cell cycle and are in “G0”

30
Q

List the checkpoints in the cell cycle

A
  • G1/S
  • G2/M
  • Metaphase/ Anaphase
  • DNA damage checkpoint
31
Q

G1/S Checkpoint

A
  • Start/ Restriction point

- Cell determines if conditions are favorable for division

32
Q

G2/M

A

Ensures all the DNA has been replicated

33
Q

Metaphase/Anaphase

A

Chromosomes are evaluated to ensure they are attached to the mitotic spindle

34
Q

DNA Damage Checkpoint

A
  • Occurs continuously throughout the cell cycle
  • Cells with damaged DNA arrest and repair
  • IF the cell cannot repair, undergoes apoptosis
35
Q

Cyclin-CDK

A
Cyclin= Regulatory subunit 
CDK= Serine/Threonine Kinase
36
Q

What mechanism degrades cyclins so they are only present at a specific point in the cell cycle?

A

Ubiquitin proteolysis

37
Q

How is CDK activity regulated?

A

Phosphorylation, Dephosphorylation & CDK Inhibitors

38
Q

c-Fos

A

Transcription factor that stimulates the transcription of the delayed response genes

39
Q

INK4

A
  • Growth Inhibitory Factors
  • Compete with Cyclin D for binding to CDK 4/6
  • Inhibit CDK 4/6
40
Q

DNA Damage Checkpoint

A
  • Requires ATM & ATR Kinases
  • ATM senses ds-DNA breaks
  • ATR senses UV damage & certain drug damage
  • Block Phosphatase Cdc25 A & C, and phosphorylate p53
41
Q

Ataxia Telangiectasia

A
  • Rare inherited disorder w/ effects on nervous & immune system
  • Ataxia= progressive balance problem
  • Telangiectasia= small widened blood vessels in skin
  • Mutation of ATM impairs cell response to ds-DNA break
  • Highly sensitive to radiation exposure