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Year 2: MCD > Cancer 4: The cell cycle and its control > Flashcards

Cancer 4: The cell cycle and its control Flashcards

1
Q

Relevance of the appropriate regulation of the cell division

A

See slides

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2
Q

Define the cell cycle

A

Orderly sequence of events in which a cell dupilcates its contents and divides into two.

Duplication
Division
Co-ordination

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3
Q

What are the two distinct phases of cell cycle?

A

M-phase: Mitosis (Division)

  • Nuclear division
  • Cell division (cytokinesis)

Interphase (duplication): Longest part of the cycle

  • DNA
  • Organelles
  • Protein synethesis
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4
Q

Which is the most vulnerable period of the cell cycle?

A

Mitosis

Cells are more easily killed (irradiation, heat shock, chemicals)
DNA damage can not be repaired
Gene transcription silenced
Metabolism?

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5
Q

Describe the eukaryotic cell cycle?

A

M phase - Mitosis

Interphase:
G0 - cell cycle machinery
	dismantled
G1 phase (Gap) - Decision point
S phase - Synthesis of DNA/protein
G2 phase (Gap) - Decision point
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6
Q

Describe the S phase

A

Replication for division

  • DNA replication
  • Protein synthesis: initiation of translation and elongation increased; capacity is also increased
  • Replication of organelles (centrosomes, mitochondria, Golgi, etc) in case of mitochondria, needs to coordinate with replication of mitochondrial DNA
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7
Q

Describe the centrosome

A

Consists of two centrioles (barrels of nine triplet microtubules)

Functions: Microtubule organizing centre (MTOC) and mitotic spindle

They are called a mother and daughter centriole

See slides for normal duplication and life cycle.

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8
Q

What are the six phases of mitosis?

A

Prophase, Prometaphase, Metaphase, Anaphase A, Anaphase B, Telophase

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9
Q

What is prophase?

A

Condensation of chromatin.

DNA wraps around nucleosomes - chromatin. Chromatin packs further and further until it reaches a fully condensed chromosome.

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10
Q

What is the centromere?

A

Belt of DNA surrounded by a kinetochore (protein complex)

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11
Q

Describe prophase

A

Condensed chromosomes - each consists of 2 sister chromatids, each with a kinetochore

  • Replicated chromosomes condense
  • Duplicated centrosomes migrate to opposite sides of the nucleus and organize the assembly of spindle microtubules
  • Mitotic spindle forms outside nucleus between the 2 centrosomes. (essential for proper mitosis)
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12
Q

Describe spindle formation

A

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

Microtubules are in a dynamic state

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13
Q

Describe metaphase?

A

Chromosomes aligned at equator of the spindle.

Early prometaphase
Late prometaphase

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14
Q

What happens in early prometaphase?

A

Breakdown of nuclear membrane

Spindle formation largely complete

Attachment of chromosomes to
spindle via kinetochores (centromere region of chromosome)

See slides for diagram.

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15
Q

What happens in late prometaphase?

A

Microtubule from opposite pole is captured by sister kinetochore

Chromosomes attached to each pole congress to the middle

Chromosome slides rapidly towards centre along microtubules

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16
Q

Describe anaphase?

A

Paired chromatids separate to form two daughter chromosomes

Cohesin holds sister chromatids together. This is broken down so that the chromatids can move apart

Two phases: Anaphase A and B

17
Q

What happens in anaphase A?

A
  • Breakdown cohesin
  • Microtubules get shorter
  • Daughter chromosomes pulled toward opposite spindle poles (start to move)
18
Q

What happens in anaphase B?

A

Two stages of movement

1) Daughter chromosomes migrate towards poles
2) Spindle poles (centrosomes) migrate apart

19
Q

Describe telophase?

A
  • Daughter chromosomes arrive at spindle
  • Nuclear envelope reassembles at each pole
  • Assembly of contractile ring
20
Q

What is cytokinesis?

A

Actin-myosin contractilce ring contracts separating the cell into two independent cells.

There are traces of the spindle called the midbody.

21
Q

Where is the mitotic checkpoint

A

Metaphase is a key mitotic checkpoint

  • Every single kinetochore needs to be attached to a microtubule.
  • Unattached kinetochores will generate signals, signalling the cell not to continue with mitosis.

BUBs protein kinases dissociate from kinetochore when chromosomes are properly attached to the spindle

When all dissociated, anaphase proceeds.

22
Q

What is a monotelic attachment?

A

When only one one spindle is attached to one side of the chromosome. See slides

23
Q

what is a syntelic attachment?

A

If both chromatids are attached to a microtubule but from the same side. See slides
This is the only attachment where the kinetochores may or may not produce a signal.

24
Q

What is a merotelic attachment?

A

If both chromatids are attached to a microtubule from their appropriate poles but one chromatid has an extra attachment from the opposite pole. See slides

25
Q

What can causes aberrant centrosome/DNA duplication

A

Monotelic, syntelic an merotelic attachments

If there is too much centrosome duplication. See slides

26
Q

Describe anti-cancer therapies by inducing gross chromsome mis-segregations?

A

Checkpoint kinase (CHKE1 and CHKE2) – Serine threonine kinase activation holds cells in G2 phase until all is ready inhibition leads to untimely cell transition to mitosis.

Taxanes and vinca alkaloids (breast and ovarian cancers)

  • Alters microtubule dynamics
  • Produces unattached kinetochores
  • Causes long-term mitotic arrest.
27
Q

What happens if something does wrong during the cell cycle? Normal pathology

A

e.g. Cell is not big enough or DNA damage

  1. Cell cycle arrest
    - at check points (G1 and spindle check point)
    - can be temporary (i.e. following DNA repair)
  2. Programmed cell death (apoptosis)
    - DNA damage too great and cannot be repaired
    1) Chromosomal abnormalities
    2) Toxic agents

Cell cycle progression aborted and cell destroyed

28
Q

What are the different cell cycle checkpoints?

A 
Metaphase checkpoint (kintechores - sister chromatids alignment)
G2 checkpoint (DNA damage)
G1 checkpoint (growth factors - tumour target this checkpoint overproduction of GF)
29
Q

Describe the deregulation of cell cycle during tumorigensis?

A

Tumours can prevent the cell from exiting the cell cycle = there is no dismantling of cell cycle apparatus

See slide 31

30
Q

Describe the signalling cascades?

A

Response to extracellular factors

Signal amplification

Signal integration

Modulation by other pathways

Regulation of divergent responses

31
Q

What happens to receptors in the presence of ligand?

A

Receptors form dimers and are activated by phosphorylation.

See slides

The phosphorylation of the receptors cause a kinase cascade
binding of adapter proteins

32
Q

Describe phosphorylation, what happens?

A

The added phosphate group (negatively charged) can alter protein function by:

  • causing a change in shape (conformation) leading to change in activity (+ve or –ve)
  • creating a docking site for another protein

Phosphate group usually added to OH group.

Serine
Threonine
Tyrosine

33
Q

Describe the protein kinase cascade?

A

See slides.

Phosphorlyation is reversed by phosphatases.
Phosphorylation by kinases

Leads to signal amplification, diversification and opportunity for regulation

Year 2: MCD (40 decks)

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