Cancer 2: The cell cycle and its control

Question 1

What happens during the M-phase of cell cycle?

Answer 1

• nuclear division

- cell division (cytokinesis)

Question 2

What happens during interphase?

Answer 2

-duplication of organelles, DNA and protein synthesis

Question 3

Why is mitosis the most vulnerable period of the cell cycle?

Answer 3

• cells more easily killed
• DNA damage not repaired
• gene transcription silenced

Question 4

What are the phases in the cell cycle?

Answer 4

• M phase = mitosis
• interphase is split up further into

G0- cell cycle machinery dismantled
G1 phase - decision point
S phase - synthesis of DNA/protein
G2 phase - decision point

Question 5

What occurs during the S phase?

Answer 5

• DNA replication
• protein synthesis - initiation of translation and elongation increased
• replication of organelles (centrosomes, mitochondria, Golgi, etc) in case of mitochondria, needs to coordinate with replication of mitochondrial DNA

Question 6

What is the centrosome?

Answer 6

-consists of two centrioles

FUNCTIONS: microtubule organizing centre and mitotic spindle

Question 7

What are the 6 phases of mitosis?

Answer 7

• prophase
• prometaphase
• metaphase
• anaphase
• telophase
• cytokinesis

Question 8

What occurs during prophase?

Answer 8

-condensation of chromatin
-duplicated centrosomes migrate to opposite sides
mitotic spindle forms outside nucleus between the 2 centrosomes
-compaction prevents damage

Question 9

What do the chromosomes look like in prophase?

Answer 9

• each is condensed and consists of 2 sister chromatids
• held at the centre by the centromere
• at this centromere there are loads of protein complexes that form the kinetochore
• kinetochore is a key regulator

Question 10

How does condensation occur in prophase?

Answer 10

• the double helicies wrap around histones, the string is then further wrapped around itself
• these fibres are then extended as a scaffold forming a chromosome scaffold

Question 11

How does spindle formation occur?

Answer 11

• radial microtubule arrays form around each centrosome
• radial arrays meet
• this changes the properties of the microtubules and polar microtubules form

Question 12

Are microtubules dynamic?

Answer 12

yes - length and shape continually change

Question 13

What can prometaphase be split into?

Answer 13

• early prometaphase

- late prometaphase

Question 14

Describe the features of early prometaphase

Answer 14

• breakdown of nuclear membrane
• spindle formation largely complete
• attachment of chromosomes to spindle via kinetochores (centromere region of chromosome)

Question 15

describe what occurs in late prometaphase

Answer 15

• microtubule from opposite pole is captures by sister kinetochore
• chromosomes attached to each pole congress to the middle
• chromosome slides rapidly towards centre along microtubules

Question 16

What defines metaphase?

Answer 16

-chromosomes aligned at the equator of the spindle

Question 17

In prometaphase what is the name of the special protein in the kinetochore that senses its attachment to microtubules?

Answer 17

-CENP-E

Question 18

What occurs in anaphase?

Answer 18

• paired chromatids separate to form two daughter chromosomes
• cohesion holds sister chromatids together

Question 19

What is specific to anaphase A?

Answer 19

• breakdown cohesion
• microtubules get shorter
• daughter chromosomes pulled toward opposite spindle poles

Question 20

What is specific to anaphase B?

Answer 20

• the spindle poles migrate apart

Question 21

What occurs in telophase?

Answer 21

• daughter chromosomes arrive at spindle
• nuclear envelope reassembles at each pole
• assembly of contractile ring

Question 22

What occurs in cytokinesis?

Answer 22

-insertion of new membrane at cleavage furrow

Question 23

How does the spindle assembly checkpoint work?

Answer 23

• senses the completion of chromosome alignment and spindle assembly
• requires CENP-E and BUB protein kinase

BUB dissociates from kinetochore when chromosomes are properly attached to the spindle and when they are all dissociated, anaphase proceeds

Question 24

How can aneuploidy occur?

Answer 24

• mis-attachment of microtubules to kinetochores

- aberrant centrosome/DNA duplication

Question 25

how is anti-cancer therapy inducing mis-segregations?

Answer 25

taxanes and vinca alkaloids alter microtubule dynamics and produce unattached kinetochores
-causes long-term mitotic arrest

Question 26

What are the options if something goes wrong during the cell cycle?

Answer 26

• cell cycle arrest at any of the checkpoints and can be temporary
• programmed cell death

this happens if the DNA damage is too great and cannot be repaired
chromosomal abnormalities
toxic agents

Question 27

What checkpoints are there in the cell cycle?

Answer 27

• during G1
• just before mitosis
• metaphase-anaphase

Question 28

How does de-regulation of the cell cycle during tumorigenesis occur?

Answer 28

tumours block the cell ability to leave the cell cycle at G0. Once they undergo mitosis they immediately enter another cycle

Question 29

What is the signalling cascade of the cell?

Answer 29

• response to extracellular factors
• signal amplification
• signal integration
• modulation by other pathways
• regulation of divergent responses

Question 30

Describe the signalling process via peptide growth factors

Answer 30

the growth factors are found in their monomeric form in their inactive state. In the presence of a ligand these form dimers

-epidermal growth factor
-platelet -derived growth factor
Receptor protein tyrosine kinase

Question 31

How can protein phosphorylation of the growth factors change their function?

Answer 31

-the added phosphate group can alter the function by causing a change in shape leading to a change in activity or creating a docking site for another protein

Question 32

What does receptor activation trigger?

Answer 32

• kinase cascades

- binding of adapter proteins