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Cancer > Cell cycle > Flashcards

Cell cycle Flashcards

Not fully complete yet - add signalling cascade

1
Q

What are the causes affecting rate of cell division

A

Embryonic vs adult Complexity of the system Necessity of renewal State of differentiation Tumour cells

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2
Q

What is the cell cycle

A

Orderly sequence of events in which a cell duplicates its contents and divides in two

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3
Q

What happens during interphase?

A

Duplication of DNA, organelles and protein synthesis

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4
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 Gene transcription silenced Metabolism slowed down

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5
Q

What are the phases of the cell cycle?

A

M phase - mitosis Interphase: G0 - cell cycle machinery dismantled G1 - decision point (checkpoint) S phase - synthesis of DNA/protein G2 - decision point

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6
Q

What happens during 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

What are centrosomes made of? Where are they?

A

Two centrioles (barrels of nine triplet microtubules)

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8
Q

What are the functions of a centrosome?

A

Microtubule organising centre Mitotic spindle

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9
Q

Describe the life cycle of centrosomes during mitosis

A

Daughter centrosome and mother centrosome splits. Each one duplicates to form two fully functional centrosomes ready to go into the cells

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10
Q

What are the six phases of mitosis?

A

Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis

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11
Q

What happens in prophase

A

Once DNA and organelles are duplicated, DNA is condensed into chromatin. Condensed chromosomes consists of 2 sister chromatids, each with a kinetochore, which provides site of attachment for spindles Duplicated centrosomes migrate to opposite sides of the cell and become MTOC (microtubule organising centre) Mitotic spindle forms between two centrosomes

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12
Q

Describe the condensation of chromatin

A

2nm DNA double helix strand coils around histone proteins to form 11nm chromatin string The nucleosomes wind tightly around each other in a 30nm fibre The 30nm fibre wraps around a scaffold to become 300-700nm scaffold associated form, which condenses to become 1400nm chromosome

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13
Q

Reasons for appropriate regulation of cell division

A

Cell death - when there is premature/aberrant mitosis Aneuploidy - due to mutations in oncogenes and tumour suppressor genes Chromosome instability Contact inhibition of growth

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14
Q

Describe spindle formation during prophase

A
  1. Radial microtubule arrays (ASTERS) form around each centrosome to form MTOC 2. Radial arrays meet 3. Polar microtubules form Polar microtubules are constantly forming and breaking, which forms a dynamic environment
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15
Q

What happens during metaphase?

A

Chromosomes align at the equator of the spindle

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16
Q

What happens during early prometaphase

A

-breakdown of nuclear membrane - completion of spindle formation - chromosome attachment via spindles to kinetochores

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17
Q

What happens during late prometaphase?

A

Microtubule from opposite pole is captured by sister kinetochore Chromosomes attached at each pole come to the middle using CENP-E (centromere protein E - kinetochore tension sensing protein)

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18
Q

What happens during anaphase?

A

Paired chromatids separate into daughter chromosomes - cohesin holding sister chromatids together During anaphase A: -cohesin is broken down - microtubules shorten and sister chromatids are pulled towards poles During anaphase B: -daughter chromosomes migrate towards the poles -centrosomes migrate apart further

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19
Q

What happens during telophase?

A

Daughter chromosome arrive at spindle Nuclear envelope reforms Contractile ring made of actin and myosin forms - this contracts to leave a mid-body

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20
Q

What is monitored in the checkpoint as the cell transitions out of metaphase

A

Chromosome alignment and spindle assembly is monitored by unattached kinetochores, that generate checkpoint signals which will not let the system advance into anaphase

21
Q

Name two proteins that allow kinetochores to detect spindle attachment

A

CENP-E

BUB protein kinases - disconnect from kinetochore when chromosome properly attaches - then go on to signal progression to anaphase

22
Q

What is an amphelic attachment?

A

Normal attachment

23
Q

What is a monotelic attachment?

A

Only one kinetochore is bound to the centrosomes

24
Q

What is a merotelic attachment?

A

Both centrosomes are bound to the same kinetochores - sister chromosome lost during cytokinesis

25
Q

What is a syntelic attachment?

A

Same centrosomes is bound to both kinetochores - will pull both sister chromosomes to one side

26
Q

What are aberrant centrosomes

A

DNA and centrosome duplication leading to too many centrosomes - often 4 and a multipolar spindle

27
Q

How are taxanes and vinca alkaloids used in anti cancer therapy

A

-alter microtubule dynamics -produce attached kinetochores -cause long term mitotic arrest leading to apoptosis of cancer cells -are checkpoint kinase inhibitors

28
Q

What does the cell do when the cell cycle goes wrong

A
  1. Cell cycle arrests - at check points -temporary; ie following DNA repair 2. Apoptosis: - when DNA damage is too great -when there are chromosomal abnormalities - when there are toxic agents
29
Q

What are the main checkpoints within a cell cycle

A

First one is during G1 and second one is before mitosis to check for DNA damage

30
Q

How do tumours progress?

A

Tumours ignore checkpoints, and blocks the ability of the cell to exit the cell cycle into G0 (quiescent phase) and thus the cell continues to divide.

31
Q

What does the signalling cascade involve?

A
  • Response to Extracellular factors
  • Signal amplification
  • Signal integration
  • Modulation via other pathways
  • Regulation of responses
32
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

33
Q

What is contact inhibition of cell growth?

A

Cells grow normally by detecting neighbouring cells

34
Q

What happens to centrosomes during G1 and S?

A

The mother and daughter centrioles separate in G1

35
Q

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

A

Nucleating sites

NOTE: nucleation is the assembly of microtubules

36
Q

What is a kinetochore?

A

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

37
Q

Descibe the arrangements of centrosomes at the end of prophase

A

They are on the opposite sides of the nucleus

38
Q

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

A

Polar microtubules

39
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

40
Q

What are the three main types of half-spindle?

A
41
Q

What keeps the sister chromatids stuck together?

A

Cohesin (protein complex)

42
Q

What is the mid-body?

A

The point where the actin-myosin contractile ring is formed

43
Q

What can cause aneuploidy?

A
  • Mitotic checkpoint defect
  • mis-attachment of the spindles (so chromatids end up at different poles than the one they should be at)
  • aberrant mitosis (production of an abnormal number of centrosomes leads to an abnormal division of the chromatids and abnormal cytokinesis)
44
Q

Explain how cell cycle checkpoints can be a target for anti-cancer therapy?

A
45
Q

Give an example of an anti cancer drug that target cell cycle checkpoints

A
46
Q

What are two extracellular factors that help in signalling in the cell cycle?

A

EGF (epidermal growth factor) and PDGF (platelet derived growth factor)

47
Q

What happens when an extracellular factor binds to the receptors?

A
  • Receptors are initially monomeric in inactive state
  • When the ligand binds to it, receptors form dimers which cause the kinase cascade
  • Tyrosine kinase domain become phosphorylated -> leading to blinding of adaptor proteins
48
Q

How does phosphorylation alter protein function

A

C

49
Q
A

Cancer (8 decks)

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