Cell Cycle

Question 1

What does the rate of cell division depend on

Answer 1

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

Question 2

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

Answer 2

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.

Question 3

Why is mitosis the most vulnerable period of the cell cycle

Answer 3

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

Question 4

What are the stages of the cell cycle

Answer 4

M phase - Mitosis

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

Question 5

What occurs in the S phase

Answer 5

Replication for division:

DNA replication

Protein synthesis: initiation of translation and elongation increased; capacity is also increased

Replication of organelles (centrosomes, mitochondria, Golgi, etc)

Question 6

What is important in the S phase replication of mitochondria

Answer 6

Needs to coordinate with replication of mitochondrial DNA

Question 7

Describe the centrosome and its functions

Answer 7

Consists of two centrioles (barrels of 9 triplet microtubules)

origin of all the microtubules of the mitotic spindle

Question 8

Describe the life cycle of centrosomes during mitosis

Answer 8

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

Question 9

What are the phases of mitosis

Answer 9

(Interphase)
Prophase
Prometaphase 
Metaphase
Anaphase
Telophase
Cytokinesis

Question 10

What occurs during prophase

Answer 10

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

Question 11

What occurs during late prophase

Answer 11

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

Question 12

What is the difference between polar and astral microtubules

Answer 12

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.

Question 13

What occurs during early pro metaphase

Answer 13

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

Question 14

What occurs during late pro metaphase

Answer 14

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

Question 15

What occurs during metaphase

Answer 15

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

Question 16

What occurs during anaphase

Answer 16

Paired chromatids separate to form two daughter chromosomes

Anaphase A and B

Question 17

What occurs during anaphase A

Answer 17

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

Question 18

What occurs during anaphase B

Answer 18

1. Daughter chromosomes migrate towards poles

2. Centrosomes also migrate apart

Question 19

What occurs during telophase

Answer 19

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

Question 20

What is the midbody

Answer 20

where the leftover microtubules overlap after telophase

Question 21

What important regulatory event occurs during the transition out of metaphase

Answer 21

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

Question 22

What does the spindle assembly checkpoint require

Answer 22

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

Question 23

What during mitosis can lead to aneuploidy

Answer 23

Mis-attachment of microtubules to kinetochores

Aberrant centrosome/DNA duplication

Question 24

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

Answer 24

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

Question 25

Describe the use of checkpoint kinase in anti-cancer therapy

Answer 25

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

Question 26

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

Answer 26

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

Question 27

What happens when and error occurs during the cell cycle

Answer 27

Cell cycle arrest | Programmed cell death

Question 28

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

Answer 28

At check points (G1 and spindle check point) | Can be temporary (i.e. following DNA repair)

Question 29

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

Answer 29

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

Question 30

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

Answer 30

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

Question 31

What does exit from G0 require

Answer 31

Growth factors and intracellular signalling cascades

Question 32

Describe the signalling cascades

Answer 32

``` Response to extracellular factors Signal amplification Signal integration Modulation by other pathways Regulation of divergent responses ```

Question 33

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

Answer 33

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

Question 34

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

Answer 34

Respective receptors found as monomeric, inactive state Receptor Protein Tyrosine Kinase (RPTK) Receptors form dimers Activated by phosphorylation

Question 35

Describe protein phosphorylation and which amino acids are targeted

Answer 35

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

Question 36

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

Answer 36

Causing a change in shape (conformation) leading to change in activity (+ve or –ve) Creating a docking site for another protein

Question 37

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

Answer 37

Triggers kinase cascades and binding of adapter proteins

Question 38

What is syntelic attachment

Answer 38

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

Question 39

What is monotelic attachment

Answer 39

one kinetochore is attached by a microtubule

Question 40

What is merotellic attachment

Answer 40

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