Cell Division Flashcards

1
Q

What is contact inhibition of cell growth?

A

Cells grow normally by detecting neighbouring cells

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2
Q

What happens during the three stages of interphase?

A

G1 – the cell makes sure that it has everything that is necessary for duplication
S – DNA replication, protein synthesis and replication of organelles
G2 – the cell checks that everything is ready to enter mitosis

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3
Q

What are centrosomes and what do they consist of?

A

Centrosomes are organelles near the nucleus of a cell, which consist of two centrioles (barrels of 9 triplet microtubules.
They form the MTOC (microtubule organising centre) and hence the mitotic spindle

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4
Q

What happens to the centrosomes during G1 and S?

A

The mother and daughter centrioles separate in G1
Then the mother produces another daughter and the daughter produces another mother, resulting in the formation of 2 centrosomes (the duplication takes place during S phase)

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5
Q

What are the points around the centrosome from which microtubules arise?

A

Nucleating sites

NOTE: nucleation is the assembly of microtubules

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6
Q

Describe the condensation of chromatin that takes place during prophase.

A
2nm DNA
11nm Chromatin string
30nm Chromatin fibre
300-700nm scaffold-associated form
1400nm Chromosome
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7
Q

What is a kinetochore?

A

Protein complexes that are attached to each sister chromatid – they are important in detecting the attachment of microtubules

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8
Q

Describe the arrangement of centrosomes at the end of prophase.

A

They are on opposite sides of the nucleus

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9
Q

What is formed when microtubule arrays from the two centrosomes meet in the middle?

A

Polar microtubules

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10
Q

What happens to the sister chromatids as soon as they are captured by microtubule arrays from both centrosomes?

A

They slide towards the middle of the cell

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11
Q

What are the three main types of half-spindle?

A

Kinetochore microtubule – attached to kinetochores
Polar microtubule – attached to a microtubule array from the other centrosome
Astral microtubule – microtubule originating from a centrosome that does not connect to a kinetochore

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12
Q

What keeps the sister chromatids stuck together?

A

Cohesin (protein complex)

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13
Q

What happens in anaphase A?

A
  1. Cohesin is broken down and the

2. Microtubules get shorter so the are chromatids pulled towards poles

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14
Q

What happens in anaphase B?

A
  1. Daughter chromatids continue to migrate towards the poles
  2. The spindle poles (centrosomes) migrate apart
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15
Q

Describe what happens in telophase.

A
  1. Daughter chromatids arrive at spindle
  2. Nuclear envelope reassembles
  3. Assembly of a contractile ring of actin and myosin filaments where the cells are going to split

The contractile ring squeezes the cell so it divides into two daughter cells
NOTE: cleavage furrow = where the cell is going to be cleaved

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16
Q

What is the midbody?

A

The point where the actin-myosin contractile ring is formed

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17
Q

Describe how the spindle assembly checkpoint works (transition out of metaphase).

A

The kinetochore has proteins that emit a signal when the kinetochore is NOT attached to microtubules

When a microtubule attaches to the kinetochore, it stops emitting the signal

At the end of metaphase, you want all the kinetochores to stop sending signals before you can proceed to anaphase

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18
Q

Name two proteins that allow the kinetochores to detect spindle attachment.

A
  1. CENP-E
  2. BUB-protein kinase (this dissociates from the kinetochores when the chromatids are properly attached to the spindle – then they go on to signal progression to anaphase)

when all dissociated anaphase proceeds

19
Q

What can cause aneuploidy?

A

Metaphase checkpoint defect

  1. Mis-attachment of the spindles (so chromatids end up at different poles to the ones that they should be at)
  2. Aberrant centrosomes (production of an abnormal number of centrosomes normally too many, 4, leads to abnormal division of the chromatids and a multipolar spindle, and abnormal cytokinesis)
20
Q

Name four different types of spindle attachment.

A
  1. Amphitelic – normal spindle attachment
  2. Syntelic – both kinetochores of the sister chromatids are attached to spindles from one centrosome
  3. Merotelic – one kinetochore of one of the sister chromatids is attached to spindles from both centrosomes
  4. Monotelic – one kinetochore of one of the sister chromatids is attached to a spindle, the other is unattached
21
Q

Broadly speaking, explain how cell cycle checkpoints can be a target for anti-cancer therapy.

A

By targeting the cell cycle checkpoints, the cancer cells can be arrested in mitosis
Cells are very vulnerable when they are in mitosis and are more easily killed

22
Q

Give an example of anti-cancer drugs that target cell cycle checkpoints.

A

Taxanes and Vinca alkaloids

These alter microtubule dynamics and produce unattached kinetochores, which leads to long-term microtubule arrest

23
Q

What can happen if something goes wrong during the cell cycle?

A
  1. Cell cycle arrest
    - at checkpoints
    - can be temporary i.e following DNA repair
  2. Apoptosis
    - DNA damage too great
    - chromosomal abnormalities
    - toxic agents
24
Q

Where are the main checkpoints within the cell cycle?

A
  1. During G1
  2. G2- DNA damage
    Just before mitosis to check for DNA damage
  3. Metaphase-anaphase checkpoint (spindle assembly checkpoint)
25
Q

What factors are responsible for cells dividing at different rates?

A
  1. Adult vs Embryonic, embryonic cells divide faster
  2. Complexity e.g yeast cells 1.5-3h
  3. Necessity for self-renewal e.g intestinal epithelia approx 20h, hepatocytes 1 year
  4. State of differentiation, neurones NEVER divide
  5. Tumour cells
26
Q

What are the reasons/ relevance of appropriate regulation of cell division?

A
  1. Cell death- when there is premature/aberrant mitosis
  2. Aneuploidy- due to mutations in oncogenes and tumour suppressor genes
  3. Chromosome instability
  4. Contact inhibition of growth
  5. Attacking the machinery that regulates chromosome segregation is one of the most successful anti-cancer strategies in clinical use
27
Q

What happens in mitosis broadly speaking?

A

M phase

  1. Nuclear division
  2. Cytokinesis (cell division)
28
Q

What happens in interphase broadly speaking?

A
  1. Duplication of DNA and organelles

2. Protein synthesis

29
Q

What is the most vulnerable part of the cell cycle and why?

A

Mitosis

  1. Cells more easily killed e.g heat shock
  2. DNA damage not repaired
  3. Gene transcription silenced
  4. Metabolism
30
Q

What are the three actions in prophase?

A
  1. Chromsome condense
  2. Duplicated centrosomes migrate to opposite sides of cell and become MTOC
  3. Mitotic spindle forms between 2 centrosomes
31
Q

Describe spindle formation in prophase

A
  1. Radial microtubule arrays (ASTERS) form around each centrosome- MTOC
  2. Radial arrays meet
  3. Polar microtubules form

(dynamic environment with polar microtubules constantly forming and breaking)

32
Q

What happens in metaphase broadly speaking?

A

chromosomes align at equator of spindle

33
Q

What is prometaphase split into?

A

Early prometaphase

Late prometaphase

34
Q

What happens in early prometaphase?

A
  1. Breakdown of nuclear membrane
  2. Spindle formation complete
  3. Chromosomes attach via spindles to kinetochores
35
Q

What happens in late prometaphase?

A
  1. Microtubule from opposite pole is captured by sister kinetochore
  2. Chromosomes attached to each pole congress to the middle
  3. Chromosome slides rapidly towards center along microtubules
    CENP relevant here.
36
Q

What triggers a cell to enter the cell cycle and divide?

A

exit from G0 (quiescent stage) requires;
1. growth factors
2. intracellular cascade
note, tumours ignore checkpoints, in absence of stimulus cells go into G0 but tumour black ability of cell into G0 hence continue to divide

37
Q

What does the signalling cascade involve?

A
  1. Response to extracellular factors
  2. Signal amplification
  3. Signal integration
  4. Modulation by other pathways
  5. Regulation of divergent responses
38
Q

Describe the signalling response to extracellular factors using EGF and PGDF.

A

EGF is epidermal growth factor
- receptors are monomeric in inactive state
- relevant receptor here is RPTK (receptor protein tyrosine kinase)
when ligand binds (in presence of ligand);
1. Receptors form dimers
2. Kinases are activated by phosphorylation
this leads to
- kinase cascade
- binding of adapter proteins

39
Q

In response to extracellular factors in signalling, what side chains can be phosphorylated?

A
  1. Serine
  2. Threonine
  3. Tyrosine

phosphate group transferred from ATP to hydroxyl OH group

40
Q

How does the addition of a phosphate group alter protein function?

A
  1. Change in conformation, thus change in activity

2. Create a docking site for another protein

41
Q

Explain the protein kinase cascade and what it leads to

A

proteins regulated by kinases are often other kinases.
therefor activation of one kinase activates another leading to;

  1. signal amplification
  2. signal diversification
  3. opportunity for regulation
42
Q

What do kinases do, and what is the opposite group of enzymes called?

A

kinases cause phosphorylation of proteins

phosphatases do the opposite; they cause removal of phosphate groups (dephosphorylation).

43
Q

What doe adaptor proteins do and give an example?

A

involved in linking two proteins together

example is Grb2