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*Y2 MCD Cancer* > Cell Cycle and its Control > Flashcards

Cell Cycle and its Control Flashcards

1
Q

What are two cell types that do not divide?

A

Neurones and Cardiac Myocytes

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2
Q

What happens when Premature, abberant mitosis occurs?

A

Cell death

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3
Q

What changes in DNA are often seen in cancer cells?

A

Mutations in Oncogenes and tumour suppressor genes

Aneuploidies

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4
Q

Why do tumours tend to keep growing?

A

They lack contact inhibition of growth - don’t sense neighbour cells

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5
Q

Why is Mitosis the most vunerable point in the cell cycle?

A

Cells are more easily killed during mitosis which is why it takes such little time

When DNA is damaged during Mitosis, it cannot be repaired

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6
Q

What are the 5 main Stages of the cell cycle?

A

Mitosis

G0 - Cell cycle machinery dismantled

G1 - Gap Phase

S - Synthesis phase

G2 - Gap Phase

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7
Q

Where are most cells in the cell cycle?

A

G0

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8
Q

What happens in the S phase?

A

DNA replication

Protein synthesis

Replication of Organelles

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9
Q

What is the centrosome?

Where is it located?

What does it consist of?

What are its functions?

A

Organelle which contains Centrioles from which the spindle fibres develop in cell division

Located near nucleus

Consists of mother and daughter centrioles (barrels of nine triplet microtubules)

Acts as Microtubule organising centre and Mitotic spindle

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10
Q

Describe the process of Centrosome replication:

A
  1. G1: Seperation of the mother and daughter centrioles
  2. S: The start to duplicate (mother produces daughter, daughter produces mother)
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11
Q

What is nucleation?

A

The polymerisation of microtubule monomers to make a long filament

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12
Q

What happens in Centrosome nucleation?

A

There is a cloud of protein complexes around the centrosomes which are nucleating sites

As the cell encounters a need for mitosis the microtubules start to grow from these points to form an array of microtubules

(look like sea urchin)

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13
Q

What are the six phases of mitosis?

A

Prophase

Prometaphase

Metaphase

Anaphase

Telophase

Cytokinesis

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14
Q

What happens in Prophase?

A

Duplicated DNA condenses (to reduce damage during mitosis)

Late Prophase: Nuclear envelope breaks down

Centrosomes migrate to opposite sides and begin to organise the spindle

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15
Q

What is the order of DNA condensation?

A
  1. Double helices wrap around histones to form beads on a string form of chromatin (from 2nm to 11nm)
  2. string further wraps around itself (30nm)
  3. A chromosome scaffold then forms (300nm)
  4. Further wrapping until chromosome (700nm then 1400nm)
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16
Q

Describe the anatomy of a chromosome:

A

Each chromosome consists of two sister chromatids

The Centromere wraps around the chromatids like a belt

Protein complexes on the centromere form the Kinetochore

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17
Q

Describe spindle formation:

A

Radial microtubule arrays (ASTERS) form around each chromosome

The radial arrays meet in the middle

Polar microtubules are formed

These form highways telling the chromosomes where to go

18
Q

What happens in early prometaphase?

A

Breakdown of nuclear envelope

Spindle formation is largely complete

Attachment of chromosomes to spindle via kinetochore

19
Q

How do spindles connect to chromosomes?

A

Each microtubule meeting in the middle needs to find a chromosome

Spindles attach via the kinetochore

One microtubule array will attach to the kinetochore on one side and another will attach on the other side

There are specialised proteins in the kinetochore that sense the attachment of microtubules

20
Q

What happens in Late Prometaphase?

A

The sister chromatids have been captured by the microtubule arrays

Once captured, the chromosomes slide rapidly towards the middle of the cell

21
Q

What are the three types of half-spindle?

A

Kinetochore microtubule - Bound to the kinetochore

Polar microtubule - a microtubule that has met and connected with a microtubule from the other centrosome

Astral Microtubule - a microtubule that is originating from the centrosome that does not connect to a kinetochore

22
Q

What happens in Anaphase?

A

Anaphase A:

Cohesin - the protein complex that holds the sister chromatids together - breaks down

The microtubules begin to shorten and the chromatids move towards the centrosomes

Anaphase B:

The daughter chromosomes reach the opposite poles - either by microtubule shortening or moving apart of centrosomes

23
Q

What happens in Telophase?

A

Daughter Chromatids reach pole

Nuclear envelops reassemble

Contractile ring of actin and myosin filaments forms

The cleavage furrow is where the cells are going to be cleaved

24
Q

What happens in Cytokinesis?

A

New membrane inserted at the cleavage furrow

Midbody is formed (Where the actin-myosin ring is formed)

Actin-Myosin ring contracts - Cytokinesis

25
Q

When is the Spindle Assembly Checkpoint?

A

After Metaphase before Anaphase can commence

26
Q

What does the Spindle Assembly checkpoint ensure?

A

Completion of Chromosome Alignment

Checks for Spindle Assembly

27
Q

How does the Spindle assembly checkpoint work?

A

Kinetochores emit a signal when the kinetochore is not attached to microtubules

When all kinetochores have microtubules bound, the signals have all stopped and anaphase can commence

28
Q

What are two proteins that are involved in the Spindle Assembly Checkpoint?

A

CENP-E

BUB Protein Kinase

BUBs dissociate from the Kinetochore when the chromatids are properly attached to the spindle - They then go on to signal progression to anaphase

29
Q

What happens if anaphase initiates before the Spindle Assembly Checkpoint?

(Mitotic Checkpoint Defect)

A

Before all the microtubules have attached, if Anaphase initiates, there will be an abnormal division of the chromosomes between the daughter cells

This results in Aneuploidy

30
Q

What are the three ways Misattachement of Microtubules to Kinetochores may occur?

(Just the names)

A

Syntelic Attachment

Merotelic Attachment

Monotelic Attachment

31
Q

What is Syntelic Attachment?

A

Both kinetochores are hooked by two microtubule arrays from the same centrosome

32
Q

What is Merotelic Attachment?

A

There is more than one microtubule array attached to the same kinetochore

  • One of the sister chromatids is being pulled in two directions
33
Q

What is Monotelic Attachment?

A

Only one of the kinetochores of one chromosome is attached to a microtubule array, the other is unattached

34
Q

What happens at cytokinesis if there has been a Merotelic attachement?

A

Chromosome loss from one of the daughter cells at cytokinesis

35
Q

What is aberrant Mitosis?

A

If the centrosomes are not duplicated properly, you could end up with 4 centrosomes in one cell

This leads to very abnormal attachment of microtubules to the kinetochores leading to abnormal cytokinesis producing 4 cells

36
Q

How can an anti-cancer therapy be used to exploit the Mitotic checkpoint?

(What types of chemotherapeutics are used and for which cancers?)

A

Taxanes and Vinca Alkaloids (Breast and Ovarian)

By inhibiting the checkpoint, you can cause the cell to proceed to anaphase before all the chromatids are attached to microtubule arrays.

By altering microtubule dynamics, long-term mitotic arrest is caused

These are more easily killed

37
Q

What happens if DNA damage is detected during the cell cycle?

A

If repairable then cell cycle is arrested whilst it is repaired

If irreversible, then apoptosis

38
Q

Where are the three main checkpoints during the cell cycle?

A

During G1

Before Mitosis (End of G2)

Metaphase-Anaphase checkpoint

39
Q

What causes cell division?

A

Exit from G0 requires growth factors and intracellular signalling cascades

40
Q

What is deregulation of the cell cycle during tumorigenesis?

A

Normally when cells exit G1 they enter G0

Tumours block the ability of the cell to enter G0; they continue to divide - cell cycle apparatus is not dismantled

*Y2 MCD Cancer* (3 decks)

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