Cell Division

Question 1

What is contact inhibition of cell growth?

Answer 1

Cells grow normally by detecting neighbouring cells

Question 2

What happens during the 3 stages of interphase?

Answer 2

G1: cell ensures it has everything necessary for duplication
S: DNA replication, protein synthesis + replication of organelles
G2: cell checks everything is ready to enter mitosis

Question 3

What are centrosomes and what is their function?

Answer 3

Consist of 2 centrioles (barrels of 9 triplet microtubules= mother + daughter) at 90 degrees
Microtubule organising center (MTOC)
Miotic spindle

Question 4

What happens to the centrosomes during G1 and S?

Answer 4

G1: Mother + daughter centrioles separate
S phase: Mother produces another daughter + daughter produces another mother, resulting in the formation of 2 centrosomes

Question 5

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

Answer 5

Nucleating sites

nucleation is the assembly of microtubules- allows for polymerisation

Question 6

Describe the condensation of chromatin that takes place during prophase.

Answer 6

Double helices wrap around histones to form beads-on-a-string
This is further compacted to form 30 nm fibres
Its then compacted to form a chromosome scaffold + further wrapped to form a chromosome (1400 nm)

Question 7

What is a kinetochore?

Answer 7

Protein complexes that are attached to each sister chromatid

important in detecting the attachment of microtubules

Question 8

Describe the arrangement of centrosomes at the end of prophase. What are they doing here?

Answer 8

On opposite sides of the nucleus.
Organising assembly of spindle microtubules
Miotic spindle forms outside the nucleus between the 2 centrosomes

Question 9

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

Answer 9

Polar microtubules

Question 10

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

Answer 10

They slide towards the middle of the cell

Question 11

What are the 3 main types of half-spindle?

Answer 11

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

Question 12

What keeps the sister chromatids stuck together?

Answer 12

Cohesin (protein complex)

Question 13

What happens in anaphase A?

Answer 13

Cohesin is broken down + microtubules shorten so chromatids start moving towards their respective poles

Question 14

What happens in anaphase B?

Answer 14

Daughter chromatids continue to migrate towards the poles

Centrosomes migrate apart

Question 15

Describe what happens in telophase.

Answer 15

Daughter chromatids arrive at the pole + nuclear envelope reassembles
Assembly of a contractile ring of actin + myosin filaments where the cell is going to split
The contractile ring squeezes the cell so it divides into 2 daughter cells
Cleavage furrow = where the cell is going to be cleaved

Question 16

What is the midbody?

Answer 16

Where the actin-myosin contractile ring is formed

Question 17

Describe how the spindle assembly checkpoint works.

Answer 17

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, want all kinetochores to stop sending signals before proceeding to anaphase

Question 18

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

Answer 18

CENP-E (senses tension of microtubules)
BUB-protein kinase (dissociates from kinetochores when chromosomes are properly attached to the spindle, then they go on to signal progression to anaphase)

Question 19

What can cause aneuploidy?

Answer 19

Mitotic checkpoint defect  :
Mis-attachment of the spindles (chromatids end up at different poles to the ones that they should be at) 
Aberrant mitosis (production of an abnormal number of centrosomes leads to abnormal division of the chromatids, + abnormal cytokinesis)

Question 20

Name 4 different types of spindle attachment.

Answer 20

Amphitelic: normal spindle attachment
Syntelic: both kinetochores of sister chromatids are attached to spindles from 1 centrosome
Merotelic: >1 spindle attached to same kinetochore
Monotelic: 1 kinetochore of 1 of the chromatids is attached to a spindle, the other is unattached

Question 21

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

Answer 21

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

Question 22

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

Answer 22

Taxanes + Vinca alkaloids

Alter microtubule dynamics + produce unattached kinetochores, which leads to long-term miotic arrest

Question 23

What can happen to cells that are held up at a checkpoint?

Answer 23

Undergo DNA repair + then proceed through the cell cycle

If damage is irreparable, they can undergo apoptosis

Question 24

Where are the main checkpoints within the cell cycle?

Answer 24

During G1
Mitosis entry: Just before mitosis to check for DNA damage
Metaphase-anaphase checkpoint (spindle assembly checkpoint, checks alignment of chromosomes)

Question 25

Why do different cells divide at different rates?

Answer 25

Embryonic divide much faster than adult
Complexity of cell
Necessity for renewal e.g. intestine undergoing constant renewal
State of differentiation e.g. some never divide- neurones
Tumours lose the ability to control proliferation

Question 26

Why is mitosis the shortest phase of mitosis?

Answer 26

Most vulnerable period
Cells more easily killed
DNA damage during can't be repaired
Gene transcription is silenced 
Metabolism is reduced, energy focused on division

Question 27

List the 6 phases of mitosis

Answer 27

Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis

Question 28

In which phase are chromosomes aligned at the equator of the spindle?

Answer 28

Metaphase

Question 29

What occurs in early pro metaphase?

Answer 29

Breakdown of nuclear membrane
Spindle formation largely complete
Attachment of chromosomes to spindle via kinetochores

Question 30

What occurs in late pro metaphase?

Answer 30

Microtubule from opposite pole is captured by sister kinetochore

Question 31

What can inhibition of attachment error-correction mechanism lead to?

Answer 31

Cell divides before chromosomes are aligned
Inviable cells
Apoptosis

Question 32

What does serine threonine kinase (checkpoint kinase) activation do? Thus, what does inhibition of this cause?

Answer 32

Holds cells in G2 phase until all is ready

Inhibition leads to untimely cell transition to mitosis + cell death

Question 33

How may tumours effect each checkpoint?

Answer 33

Upregulation of growth factors/ receptors increasing the speed of the cycle
Blockade of entry to mitosis checkpoint, so cell enters mitosis before it is ready
Blockade of alignment checkpoint: causes loss/ gain of chromosomes
Blockade of exit from cycle

Question 34

How do growth factors activate a cell? What does receptor activation trigger?

Answer 34

GFs are dimeric, bind to 2 receptors.
Once in close proximity, the tyrosine kinase domains cross phosphorylate each other, becoming activated
Triggers kinase cascades + binding of adapter proteins

Question 35

How does phosphorylation alter protein function?

Answer 35

Causes conformational change leading to change in activity

Creates docking site for another protein

Question 36

What is the significance of protein kinase cascades?

Answer 36

Leads to signal amplification, diversification + opportunity for regulation

Question 37

What is phosphorylation reversed by?

Answer 37

Phosphatases