Cell Replication

Question 1

Define and describe the cytoskeleton

Answer 1

The cytoskeleton is comprised of fibrous proteins of varying diameter, each with specific functions. The cytoskeleton uses their proteins to: Support the cell, Move the cell (e.g. in cell migration), For the movement of organelles within the cell. The three major proteins within the cytoskelton are: Actin filaments, Intermediate filaments and Microtubules.

Question 2

Define and describe microtubules

Answer 2

Microtubules are polymers of α and β tubulin heterodimers, with a thickness of around 25 nm. They act as “tracks” for the movement of organelles and other cytoplasmic components within the cell. Microtubules often radiate from a central structure in a cell known as the microtubule organising centre (MTOC). Microtubules play key roles in the process of mitosis, notably in the formation of the mitotic spindle which guides the organisation and separation of the chromosomes

Question 3

What impacts cell division time?

Answer 3

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

Question 4

Why does cell division need to be regulated?

Answer 4

1. Premature aberrant mitosis results in cell death
2. In addition to mutations in oncogenes and tumour suppressor genes, most solid tumours are aneuploid
3. Various cancer cell lines show chromosome instability (lose and gain whole chromosomes during cell division
4. Perturbation of protein levels of cell cycle regulators is found in different tumours; abnormal mitosis
5. Contact inhibition of growth - when cells grow, fill in space they need to then they stop; tumour cells don’t have this - don’t recognise neighbours and stop like normal cells

Question 5

What is the cell cycle and what are its stages?

Answer 5

Orderly sequence of events in which a cell duplicates it’s contents and divides in two. Sequence is duplication, division and coordination. Individual cell has chromosomes replicate then segragate and finally division.

Question 6

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

Answer 6

1. Cells more easily killed (irradiation; heat shock; chemicals)
2. DNA damage cannot be repaired
3. Gene transcription; no new mRNA or proteins

Question 7

What are the stages of interphase?

Answer 7

G0 - Quiescent state (cell cycle machinery dismantled)
G1- decision where it decides if it had conditions to go there
S - synthesis of all the proteins and organelles
G2- check if everything is duplicated etc.

Question 8

Describe DNA replication in the cell cycle

Answer 8

1. Protein Synthesis: initation of translation and elongation increased; capacity is also increased
2. Replication of organelles: centrosomes; mitochondria; Golgi etc
3. Mitochondria replication needs to coordinate with the replication of mitochondrial DNA

Question 9

What is the centrosome?

Answer 9

Comprises two centrioles
Barrels of nine triplet microtubules
Function: microtubules organising centre MTOC
Organise mitotic spindle
Resides by nuclues
Life cycle of centrosome: Separate during G1, replicate during S

Question 10

What are the 6 stages of the cell cycle?

Answer 10

Interphase, Prophase, Metaphase, Anaphase, Telophase, Cytokinesis

Question 11

What happens in prophase?

Answer 11

DNA double helix (2nm) associates with histones to form the beads on a string form of chromatin (11nm) These wrap into themselves; 30nm chromatin fiber of packed nucleosomes formed. These then hook into extended scaffold-associated form and pack themselves again; condensed and scaffold-associated, forming a condensed chromosome. Allows the chromosomes to move around cell without too much damage.

Question 12

What are the two stages of prophase?

Answer 12

In prophase 1, condensed chromosomes comprise two sister chromatids held together at the centromere by a kinetochore; this allows for control of how they divide between the cells. In Prophase 2, the replicated chromosomes condense and duplicated chromosomes migrate to opposite sides of the nucleus. Mitotic spindle forms outside nucleus between 2 centrosomes.

Question 13

How does mitotic spindle form?

Answer 13

Radial microtubule arrays (ASTERS) form around each centrosome grown from MTOC (microtubule organising centre). Where these radial arrays meet, polar microtubules formed.

Question 14

What happens during early prometaphase?

Answer 14

Breakdown of nuclear membrane, Spindle formation largely complete, Attachment of chromosomes to spindle fibres via kinetocores (centromere region of chromosomes), Finding the sister chromosomes

Question 15

What happens during late prometaphase?

Answer 15

Microtubule from opposite pole is captured by sister kinetochore, Chromosomes attached to each pole congress to the middle, Chromosome slides rapidly towards centre along microtubules
CENP-E - tension sensing; checking if everything is connected (important check before anaphase)

Question 16

What happens during anaphase?

Answer 16

Cohesin holds sister chromatids together. Anaphase is divided into two stages: Anaphase A is when cohesin breaks down, the microtubules get shorter and hence daughter chromosomes are pulled towards the opposite spindle poles. During anaphase B, daughter chromosomes migrate towards poles. 
Spindle poles (centrosomes) migrate apart. This is important so that when the cell pinches, the DNA for each new cell has a clear distance between them.

Question 17

What happens during telophase?

Answer 17

Daughter chromosomes arrive at spindle. Nuclear envelope reassembles at each pole. Assembly of contractile ring.

Question 18

What are the two possible outcomes of something going wrong during the cell cycle?

Answer 18

Cell cycle arrest or Apoptosis (programmed cell death). Cell cycle arrest occurs at checkpoints (G1 and spindle check point) and can be temporary (ie following DNA repair). Apoptosis occurs when DNA damage is too great and cannot be repaired such as chromosomal abnormalities or presence of toxic agents.

Question 19

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

Answer 19

In the absence of stimulus, cells go into quiescent phase (G0). Most cells which are differentiated for a specific function remain in this stage. These cells are not dormant, but simply not dividing. The exit from G0 is highly regulated as it requires signals from growth factors and intracellular signalling cascades.

Question 20

What do intracellular signalling cascades do?

Answer 20

Response to extracellular factors, Signal amplification, Signal integration, Modulation by other pathways and Regulation of divergent reponses.