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Cell Biology > Quiescence and Senescence > Flashcards

Quiescence and Senescence Flashcards

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1
Q

What is free living cell growth regulated by?

What about cell growth in multicellular animals?

A

Environmental cues e.g. nutrient supply

Extracellular signals

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2
Q

What is apoptosis?

A

Programmed cell death

- avoids further damage to surrounding cells + tissues

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3
Q

What is necrosis?

A

Unplanned cell death

  • response to damage/infection
  • can cause further damage to surrounding cells + tissues
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4
Q

Why are the cell cycle checkpoints needed?

i.e. what are the bad things that could happen in each stage?

A

G1 - DNA damage
- unfavourable extracellular environment

S - incomplete replication

G2 - insufficient cell growth

M - chromosome incorrectly attached to mitotic spindle

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5
Q

What regulates the cell cycle checkpoints?

A

Cyclin/CDK complexes

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6
Q

How are cyclin/CDK complexes dynamic?

A

CDK = present throughout cell cycle

Regulatory cyclins oscillate between synthesised state + destructed state

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7
Q

What happens when S-cyclin binds to CDK?

What happens when M-cyclin binds to CDK?

A

At G1/S checkpoint
-> triggers DNA replication machinery

At G2/M checkpoint
-> triggers mitosis machinery

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8
Q

What does a peak in CDK activity result from?

What happens at this point?

What happens after this?

A

Steady accumulation of cyclin

Mitosis occurs

Rapid destruction of cyclin
-> decrease in M-CDK activity
= interphase

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9
Q

Explain how cyclin accumulates

A
  1. Inhibitory kinase (Wee1) phosphorylates cyclin
    = keeps it inactive
  2. Activating phosphatase (Cdc25)removes inhibitory phosphates
  3. Active cylinder/CDL phosphorylates Cdc25
    (+ve feedback)
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10
Q

How can you identify mutants that have passed through the cell cycle too quickly?

A

V small

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11
Q

Explain how cyclin levels decrease

A

APC (anaphase promoting complex) adds chains of ubiquitin molecules to cyclin proteins
= tags them for rapid destruction at proteosomes

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12
Q

What does the G1/S phase checkpoint prevent?

A

Replication of damaged DNA

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13
Q

How does the G1/S checkpoint prevent replication of damaged DNA?

A
  1. X-rays damage DNA
  2. Activates protein kinases
    -> phosphorylate + activate p53
  3. p53 acts as a TF
    -> binds to regulatory region of p21 gene
  4. p21 transcribed + translated
  5. p21 binds to CDK complexes
    = inactivates them
  6. Allows time for cell to repair damaged DNA or undergo apoptosis
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14
Q

What are the 2 roles of p53?

A

Transcription factor

Tumour suppressor

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15
Q

What happens if there is no DNA damage?

A

p53 is degraded in proteosomes

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16
Q

What happens in cell cycle withdrawal?

A

Cells instructed to exit cell cycle and…:
> undergo apoptosis
> enter G0

17
Q

How are cells instructed to enter G0?

A

Absence of proliferation signals

Presence of -ve regulators

18
Q

What is quiescence?

A

Cells in G0 phase but have the capacity to re-enter the cell cycle when appropriate

19
Q

How does Rb control cell proliferation in resting cells?

A

Rb sequesters TFs essential for initiating DNA replication + nucleotide metabolism at the start of S phase

20
Q

How does Rb control cell proliferation in proliferating cells?

A

Mitogen signals simulate synthesis of G1 cyclin
-> active G1/S cyclin/CDK complex accumulates

  • > phosphorylates Rb
  • > alters Rb conformation
  • > promotes release of TFs that promotes initiation of S phase
  • > cell proliferation
21
Q

What are the 2 roles of mitogen signals in cell proliferation?

A

> Promote cyclin synthesis

> Promote degradation of kinase inhibitory proteins e.g. Cdc25

22
Q

What are terminally differentiated cells?

Give examples

A

Specialised cells unable to proliferate

Neurons
Keratinocytes in skin
Goblet + enterocytes

23
Q

What is senescence?

Which cells evade this?

What are they known as?

A

Cells that have lost the capacity to proliferate
- can only divide a finite no. of times

Cancer cells

Immortalised/Transformed

24
Q

What are the contributing factors to senescence?

A

> accumulation of KIPs/CIPs w/ successive divisions

> shortening of telomeres

Cell Biology (23 decks)

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