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Cellular Biology and Biochemistry > Cell growth and proliferation > Flashcards

Cell growth and proliferation Flashcards

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1
Q

Why are cell numbers controlled?

A

Loss of control can lead to diseases such as cancer

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2
Q

How are cell numbers controlled?

A

Cells divide (proliferate) when the body needs them and die when the body doesnt

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3
Q

Why is cell proliferation important?

A

Early development - required at fertilisation as a single cell proliferates into an organism with 10^14 cells

Adult life:
Tissue maintenance
Skin and gut cells replaced
Repairing damaged wounds
Replace cells when they die
Adapt to the environment
Fight infection
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4
Q

Can any cell divide?

A

Most mature cells lose the ability to divide on their own

Differentiated cells must be replaced from precursors (stem cells)

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5
Q

What are stem cells?

A

Present in small numbers in tissues

Precursors to mature cells which can differentiate into any somatic cell

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6
Q

What is the self renewal property of stem cells?

A

As a stem cell differentiates into a somatic cell

it divides in two where one cell is the cell becoming the new cell type and the other cell will become another stem cell

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7
Q

What is the self renewal property of stem cells important?

A

Ensures we have constant supply of stem cells

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8
Q

What stimulates cell proliferation?

A

Mitogenic signals from surrounding tissues

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9
Q

What properties doe growth factors posses?

A

Both growth and mitogenic activities

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10
Q

What is cell growth?

A

Cells increase in size and increase in cytoplasmic organelles

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11
Q

What is cell division?

A

Chromosome duplication,
Mitosis,
Cytokinesis

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12
Q

What is cell proliferation?

A

Cell growth + cell division

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13
Q

How do cells proliferate?

A

Via the cell cycle

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14
Q

What is interphase?

A

G1 + S + G2

Cells grow and the nuclear DNA is duplicated

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15
Q

What is mitosis and cytokinesis?

A

The nucleus and cytoplasm divide to form 2 daughter cells

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16
Q

What are the regulators of the cell cycle?

A

Cyclin dependent kinases (Cdks)

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17
Q

What are Cdks?

A

Heterodimeric proteins of two subunits

Catalytic subunit
Regulatory subunit

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18
Q

What do Cdks do?

A

Phosphorylate proteins important during specific cell cycle phases

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19
Q

When is the Cdk subunit activated?

A

When it is bound to a specific cyclin subunit

Different Cyclin-Cdk dimers regulate each cell cycle pass

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20
Q

What are the main Cdks in the cell cycle?

A

C1/S-Cdk - Starts G1 phase

S-Cdk - Regulates movement into S phase

M-Cdk - Regulates movement from G2 into mitosis

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21
Q

What are the essential steps during the cell cycle?

A
  1. Increase cell size + cytoplasmic organelles (from G1)
  2. Overcome the Restriction Point (G1)
  3. Replicate the chromosomes once, and once only (S)
  4. Make sure chromosomes are fully duplicated (G2)
  5. Separate the duplicated chromosomes (M)
  6. Separate the two daughter cells (cytokinesis)
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22
Q

What happens during G1?

A

Cells grow in size during interphase by growth factors stimulating protein synthesis

Organelles expand or increase in number

23
Q

What is the restriction checkpoint (R) in G1?

A

The checkpoint which cells can only progress through if appropriately stimulated by mitogens

24
Q

What is G0?

A

Quiescent phase where cells enter when growth factors are limiting and not stimulating progression.

25
Q

What is required for cells to progress through the Restriction point of G1?

A

Mitogenic growth factor signalling

Once through the R point, then further signalling is no longer needed

26
Q

What is the process of how cells get through the restriction point?

A
  1. Mitogenic Growth Factor signalling induces transcription of Cyclin D
  2. Cyclin D protein combines with Cdk4/6 to form G1-Cdk
  3. G1-Cdk monophosphorylates pRb
  4. G1/S-Cdk hyperphosphorylates pRb in a feedback loop to completely inactivate it
  5. Phosphorylated pRb releases E2F which induces transcription of genes required for S phase
  6. The cell can now pass through to S phase
27
Q

Which protein is hyperphosphorylated during G1?

A

Retinoblastoma Protein (pRb)

28
Q

What happens if pRb is not phosphorylated?

A

Unphosphorylated pRb binds to the E2F transcription factor to repress cell cycle gene transcription.

29
Q

What is the overall role of pRb?

A

Acts a R checkpoint to ensure that cells duplicate their chromosomes only when they are stimulated by mitogens.

30
Q

What happens in S phase?

A

The chromosomes are replicated once and only once.

31
Q

How does S phase ensure chromosomes are only replicated once?

A
  1. Pre-replicative complexes can only form at origins in G1 when Cdk activity is low
  2. Each origin fires once only in S phase in response to S-Cdk
  3. Each chromosome is replicated once only
  4. Origins are re-primed for replication only after mitosis & cell division
32
Q

What is the G2 checkpoint?

A

Ensures cells cannot enter mitosis until the chromosomes are completely replicated in S phase

Cells are held here until this happens

33
Q

What occurs at the G2 checkpoint?

A

M-Cdk is inactive preventing cells entering mitosis

Before replication is completed in S phase, Wee1 inhibitory enzyme phosphorylates Cdk-1 inactivating it

Once all chromosomes are replicated a phosphatase is activated to remove the inhibitory phosphate group off Cdk-1 reactivating it.

This then activates Cyclin B (M-cyclin) which releases the checkpoint

34
Q

What are the stages of mitosis?

A

Prophase/Prometaphase
Metaphase
Anaphase
Telophase

Cytokinesis

35
Q

What happens during prophase?

A

2 sister chromosomes duplicated in S phase are held together and condense to form chromatids

Central region of chromatics forms a kinetochore

Mitotic spindles form outside the nucleus between two spindle poles

36
Q

What happens during prometaphase?

A

breakdown of the nuclear envelope

Mitotic spindles attach to kinetochores

37
Q

What happens during metaphase?

A

Mitotic spindles link kinetochores to spindle poles to align the chromatids

38
Q

What happens during anaphase?

A

Chromosome separation at anaphase starts when all kinetochores have attached to spindle

When all kinetochores are attached the APC is activated and the cohesins break down

Chromosomes are pulled apart towards opposite poles

39
Q

What is the mitotic checkpoint?

A

Sends a stop signal when chromosomes have an unattached kinetochore to prevent the onset of anaphase.

When the kinetochores are attached the APC is activated.

40
Q

What happens during telophase?

A

Daughter chromosomes reach opposite poles of the cell

Nuclear envelope reassembles around the sets of chromosomes to from distinct nuclei

Chromosomes decondense

41
Q

What happens during cytokinesis?

A

A cleavage furrow is formed by the action of contractile rings which contract separating the daughter cells

42
Q

What happens if a cell cycle checkpoint fails?

A

Leads to un-ordered cell cycle progression

43
Q

What happens if the R checkpoint fails?

A

cells would enter S phase and replicate their chromosome without appropriate mitogenic signalling

Proliferation would be uncontrolled and lead to cancer

44
Q

What happens if the G2 checkpoint fails?

A

cells would enter mitosis with incompletely replicated genomes

Causing gene loss or mutation

45
Q

What happens if the M checkpoint fails?

A

chromosomes would not be properly segregated into the daughter cells

Cause altered chromosome number = Aneuploidy

46
Q

How are checkpoints induced?

A

Induced by DNA damage

47
Q

What happens when there is DNA damage?

A
  1. DNA damage stabilises p53 (transcription factor)
  2. p53 induces transcription of p21
  3. p21 binds and inactivates G1/S-Cdk, S-Cdk, M-Cdk
  4. Cell cycle is arrested at multiple points
  5. Prevents damaged chromosomes from being replicated
48
Q

What is p21?

A

Cdk inhibitor which arrests the cell cycle and prevents damaged chromosomes from being replicated

49
Q

What is apoptosis?

A

Programmed cell death

Digestion of cellular proteins and DNA

50
Q

What is Necrosis?

A

Accidental cell death

51
Q

Why is apoptosis important in early development?

A

Sculpt structures during morphogenesis such as digits

52
Q

Why is apoptosis important in the body?

A

When cells are no longer needed

When cells are dangerous (infected, autoimmunity)

Following irreversible cell damage

53
Q

How does apoptosis work?

A

When apoptosis is induced:

Caspases are activated

Initiator caspases are activated
These activate executioner caspases by prodomain cleavage
Executioner caspases degrade nucelar and cytosolic proteins
Phagocytes remove dead cells

54
Q

How are caspases activated?

A

Synthesised in their procaspase form

Cleavage of prodomains activates the molecule

Cellular Biology and Biochemistry (22 decks)

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