Cell Cycle and its Control

Question 1

What are two cell types that do not divide?

Answer 1

Neurones and Cardiac Myocytes

Question 2

What happens when Premature, abberant mitosis occurs?

Answer 2

Cell death

Question 3

What changes in DNA are often seen in cancer cells?

Answer 3

Mutations in Oncogenes and tumour suppressor genes

Aneuploidies

Question 4

Why do tumours tend to keep growing?

Answer 4

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

Question 5

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

Answer 5

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

Question 6

What are the 5 main Stages of the cell cycle?

Answer 6

Mitosis

G₀ - Cell cycle machinery dismantled

G₁ - Gap Phase

S - Synthesis phase

G₂ - Gap Phase

Question 7

Where are most cells in the cell cycle?

Answer 7

G₀

Question 8

What happens in the S phase?

Answer 8

DNA replication

Protein synthesis

Replication of Organelles

Question 9

What is the centrosome?

Where is it located?

What does it consist of?

What are its functions?

Answer 9

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

Question 10

Describe the process of Centrosome replication:

Answer 10

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

Question 11

What is nucleation?

Answer 11

The polymerisation of microtubule monomers to make a long filament

Question 12

What happens in Centrosome nucleation?

Answer 12

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)

Question 13

What are the six phases of mitosis?

Answer 13

Prophase

Prometaphase

Metaphase

Anaphase

Telophase

Cytokinesis

Question 14

What happens in Prophase?

Answer 14

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

Question 15

What is the order of DNA condensation?

Answer 15

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)

Question 16

Describe the anatomy of a chromosome:

Answer 16

Each chromosome consists of two sister chromatids

The Centromere wraps around the chromatids like a belt

Protein complexes on the centromere form the Kinetochore

Question 17

Describe spindle formation:

Answer 17

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

Question 18

What happens in early prometaphase?

Answer 18

Breakdown of nuclear envelope

Spindle formation is largely complete

Attachment of chromosomes to spindle via kinetochore

Question 19

How do spindles connect to chromosomes?

Answer 19

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

Question 20

What happens in Late Prometaphase?

Answer 20

The sister chromatids have been captured by the microtubule arrays

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

Question 21

What are the three types of half-spindle?

Answer 21

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

Question 22

What happens in Anaphase?

Answer 22

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

Question 23

What happens in Telophase?

Answer 23

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

Question 24

What happens in Cytokinesis?

Answer 24

New membrane inserted at the cleavage furrow

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

Actin-Myosin ring contracts - Cytokinesis

Question 25

When is the Spindle Assembly Checkpoint?

Answer 25

After Metaphase before Anaphase can commence

Question 26

What does the Spindle Assembly checkpoint ensure?

Answer 26

Completion of Chromosome Alignment Checks for Spindle Assembly

Question 27

How does the Spindle assembly checkpoint work?

Answer 27

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

Question 28

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

Answer 28

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

Question 29

What happens if anaphase initiates before the Spindle Assembly Checkpoint? (Mitotic Checkpoint Defect)

Answer 29

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

Question 30

What are the three ways Misattachement of Microtubules to Kinetochores may occur? (Just the names)

Answer 30

Syntelic Attachment Merotelic Attachment Monotelic Attachment

Question 31

What is Syntelic Attachment?

Answer 31

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

Question 32

What is Merotelic Attachment?

Answer 32

There is more than one microtubule array attached to the same kinetochore - One of the sister chromatids is being pulled in two directions

Question 33

What is Monotelic Attachment?

Answer 33

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

Question 34

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

Answer 34

Chromosome loss from one of the daughter cells at cytokinesis

Question 35

What is aberrant Mitosis?

Answer 35

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

Question 36

How can an anti-cancer therapy be used to exploit the Mitotic checkpoint? (What types of chemotherapeutics are used and for which cancers?)

Answer 36

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

Question 37

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

Answer 37

If repairable then cell cycle is arrested whilst it is repaired If irreversible, then apoptosis

Question 38

Where are the three main checkpoints during the cell cycle?

Answer 38

During G1 Before Mitosis (End of G2) Metaphase-Anaphase checkpoint

Question 39

What causes cell division?

Answer 39

Exit from G₀ requires growth factors and intracellular signalling cascades

Question 40

What is deregulation of the cell cycle during tumorigenesis?

Answer 40

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