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Y2 Cancer > Cell Cycle > Flashcards

Cell Cycle Flashcards

1
Q

What does the rate of cell division depend on

A 
Embryonic vs adult cells
Complexity of system 
Necessity for renewal 
State of differentiation 
Tumour cells
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2
Q

What is the relevance of the appropriate regulation of the cell division

A

Premature, aberrant mitosis results in cell death

Most tumours are aneuploid (have an abnormal chromosome number as well as content)

Tumour cells lose contact inhibition of growth, where if a cell is touching other cells (has no space to reproduce) then it won’t.

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3
Q

Why is mitosis the most vulnerable period of the cell cycle

A

Cells are more easily killed (irradiation, heat shock, chemicals)
DNA damage can not be repaired
no genes are being transcribed, as they’re being packed and separated
very little other metabolism is occurring due to the energy requirements of mitosis

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4
Q

What are the stages of the cell cycle

A

M phase - Mitosis

Interphase
G0 - cell cycle machinery dismantled 
G1 - decision point 
S - synthesis of DNA/protein 
G2 - Decision point
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5
Q

What occurs in 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)

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6
Q

What is important in the S phase replication of mitochondria

A

Needs to coordinate with replication of mitochondrial DNA

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7
Q

Describe the centrosome and its functions

A

Consists of two centrioles (barrels of 9 triplet microtubules)

origin of all the microtubules of the mitotic spindle

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8
Q

Describe the life cycle of centrosomes during mitosis

A

During late G1, the centrioles split and each one later goes on to duplicate, forming its own centrosome. This is a prerequisite for mitosis.

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9
Q

What are the phases of mitosis

A 
(Interphase)
Prophase
Prometaphase 
Metaphase
Anaphase
Telophase
Cytokinesis
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10
Q

What occurs during prophase

A

Condensation of chromatin
Each condensed chromosome consists of 2 sister chromatids joined at the centromere, each with a kinetochore
Nuclear envelope begins to break down

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11
Q

What occurs during late prophase

A
  1. Duplicated centrosomes migrate to opposite sides of the nucleus
  2. Centrosomes organise the assembly of spindle microtubules
  3. Radial microtubule arrays (ASTERS) form around each centrosome (microtubule organizing centers - MTOC)
  4. Polar microtubule formation
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12
Q

What is the difference between polar and astral microtubules

A

Radial microtubules from each centrosome which meet in the middle of the cell form polar microtubules.
The ones that don’t go towards the middle are called astral microtubules.

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13
Q

What occurs during early pro metaphase

A
  1. Breakdown of nuclear membrane
  2. Spindle formation largely complete
  3. Attachment of chromosomes to spindle via kinetochores (centromere region of chromosome)
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14
Q

What occurs during late pro metaphase

A
  1. Chromosome slides rapidly towards center along microtubules
  2. Chromosomes attached to each pole congress to the middle
  3. Microtubule from opposite pole is captured by sister kinetochore
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15
Q

What occurs during metaphase

A 
Chromosomes aligned at equator of the spindle
First checkpoint (spindle assembly/mitotic/M checkpoint)
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16
Q

What occurs during anaphase

A

Paired chromatids separate to form two daughter chromosomes

Anaphase A and B

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17
Q

What occurs during anaphase A

A
  1. Breakdown cohesin (which was holding the sister chromatids together)
  2. Microtubules get shorter
  3. Daughter chromosomes pulled toward opposite spindle poles
18
Q

What occurs during anaphase B

A
  1. Daughter chromosomes migrate towards poles

2. Centrosomes also migrate apart

19
Q

What occurs during telophase

A
  1. Daughter chromosomes arrive at spindle
  2. Nuclear envelope reassembles at each pole
  3. Assembly of contractile/myosin ring to create a cleavage furrow
  4. As the ring contracts, a new membrane Is inserted
20
Q

What is the midbody

A

where the leftover microtubules overlap after telophase

21
Q

What important regulatory event occurs during the transition out of metaphase

A

Spindle assembly checkpoint
Sensed completion of chromosome alignment and spindle assembly (minters kinetochore activity)
When all dissociated, anaphase proceeds.

22
Q

What does the spindle assembly checkpoint require

A

CENP-E
BUB protein kinases

BUBs dissociate from kinetochore when chromosomes are properly attached to the spindle
CENP-E (centromere protein E) checks that all the chromosomes are connected to it

23
Q

What during mitosis can lead to aneuploidy

A

Mis-attachment of microtubules to kinetochores

Aberrant centrosome/DNA duplication

24
Q

What are the different ways in which there can be mis-attachment of microtubules to kinetochores

A 
Cohesion defects/synthetic attachment
Merotelic attachment (chromatid attached to both centrosomes via both sides of kinetochore) which would not produce a checkpoint signal
25
Q

Describe the use of checkpoint kinase in anti-cancer therapy

A

Induces gross chromosome mis-segregation
Holds cells in G2 phase until they are all ready
Inhibition leads to untimely cell transition to mitosis
Knases - CHKE1 and CHKE2

26
Q

Describe the use of taxanes and vinca alkaloids in anti-cancer therapy

A

Induces gross chromosome mis-segregation in breast and ovarian cancers
Alters microtubule dynamics
Produces unattached kinetochores
Causes long-term mitotic arrest.

27
Q

What happens when and error occurs during the cell cycle

A

Cell cycle arrest

Programmed cell death

28
Q

Describe cell cycle arrest when there is an error during the cell cycle

A

At check points (G1 and spindle check point)

Can be temporary (i.e. following DNA repair)

29
Q

Describe programmed cell death when there is an error during the cell cycle

A

DNA damage too great and cannot be repaired
Chromosomal abnormalities
Toxic agents

30
Q

What happens when a cell is not simulated to enter the cell cycle

A

In the absence of stimulus, cells go into Go (quiescent phase)
Most cells in the body which are differentiated to perform specific functions
Cells are not dormant, but are non-dividing

31
Q

What does exit from G0 require

A

Growth factors and intracellular signalling cascades

32
Q

Describe the signalling cascades

A 
Response to extracellular factors
Signal amplification
Signal integration
Modulation by other pathways
Regulation of divergent responses
33
Q

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

A

Signalling by peptide growth factors: Ligand binds and activates the receptor
Ligands: Epidermal growth factor (EGF); Platelet-derived growth factor (PDGF)

34
Q

Describe the receptors involved in signalling cascades and what they do in the presence of ligand

A

Respective receptors found as monomeric, inactive state
Receptor Protein Tyrosine Kinase (RPTK)

Receptors form dimers
Activated by phosphorylation

35
Q

Describe protein phosphorylation and which amino acids are targeted

A

Transfer of phosphate from ATP to a hydroxyl groups
Serine
Threonine
Tyrosine

36
Q

What are the ways in which an added phosphate group (-ve charge) can alter protein function

A

Causing a change in shape (conformation) leading to change in activity (+ve or –ve)

Creating a docking site for another protein

37
Q

What occurs when there is signalling by peptide growth factors during receptor activation

A

Triggers kinase cascades and binding of adapter proteins

38
Q

What is syntelic attachment

A

kinetochore is attached to microtubules of the same centrosome. Both sister chromatids end up at the same pole

39
Q

What is monotelic attachment

A

one kinetochore is attached by a microtubule

40
Q

What is merotellic attachment

A

more than on microtubule attaching to the same kinetochore, leads to loss of sister chromatid

Y2 Cancer (16 decks)

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