Mitosis and regulation

Question 1

What are the stages of mitosis?

Answer 1

Prophase/propmetaphase
Metaphase
Anaphase
Telophase
Cytokinesis

Question 2

What is prophase?

Answer 2

Chromosome condensation
Nuclear envelope breakdown
Spindle formation and attachment to kinetochores.
Appearance of visible chromosomes.

Question 3

What is metaphase?

Answer 3

Chromosomes align between the two spindle poles.

Question 4

What is anaphase?

Answer 4

Chromosome separation

Question 5

What is telophase?

Answer 5

Nuclear envelope reformation
Chromosome decondensation

Question 6

What is cytokinesis?

Answer 6

Contractile (actin) ring separates new cells.

Question 7

What happens in prophase?

Answer 7

The two sister chromosomes duplicated in S phase are held together and condense to form chromatids.
The central region of the chromatids - the centromere - forms a structure called the kinetochore.
The kinetochore provides a docking point for microtubules to attach from the spindle poles, and binds to the chromosomes.

Question 8

What happens in prometaphase?

Answer 8

Starts with breakdown of the nucleus.
Mitotic spindles can now start to attach to kinetochores.

Question 9

What is the metaphase-anaphase transition?

Answer 9

In metaphase mitotic spindles (microtubules) link kinetochores to spindle poles to align chromatids.
Chromosome separation at anaphase starts when all kinetochores have an attached mitotic spindle.

Question 10

What is the mitotic checkpoint?

Answer 10

Chromosomes with an unattached kinetochore send a stop signal to prevent the onset of anaphase.
When all kinetochores are attached, the Anaphase Promoting Complex (APC) is activated.
APC activation results in the destruction of proteins - cohesins - holding sister chromatids together.
Chromosomes can then move to opposite poles in anaphase.

Question 11

What happens in telophase?

Answer 11

Daughter chromsomes reach the opposite ends of the cell.
The nuclear envelope reassembles around the sets of chromosomes to form two distinct nuclei.
Chromosomes decondense.
Spindle apparatus is lost.
The cell then divides by cytokinesis.

Question 12

What happens in cytokinesis?

Answer 12

The two nascent nuclei and cytoplasmic components are divided into daughter cells.
A cleavage furrow is formed by the action of an actin contractile ring.
This then contracts further to separate the daughter cells.

Question 13

What happens if the R point fails?

Answer 13

Cells would enter the S phase and replicate their chromosome without appropriate mitogenic signalling.
Proliferation would be uncontrolled leading to cancer.

Question 14

What happens if the G2 checkpoint fails?

Answer 14

Cells would enter mitosis with incompletely replicated genomes.
Leads to gene loss and or mutation.

Question 15

What happens if the mitotic checkpoint fails?

Answer 15

Chromosomes would not be properly segregated into the daughter cells.
Leads to altered chromosome number - aneuploidy and triploidy.
Could affect cancer critical genes.

Question 16

How do checkpoints protect against DNA damage?

Answer 16

Checkpoints are induced by DNA damage - UV light, gamma radiation, oxidising agents - smoking and air pollution, inflammation producing free radicals.
Checkpoints allow time for damage to be repaired before cell division.

Question 17

What is p53?

Answer 17

DNA damage induces expression of p53.
Transcription factor, induces expression of p21.
Binds to cyclin kinases and block activity of Cdks.

Question 18

What is p21?

Answer 18

Cdk inhibitor - can bind and inactivates all cyclin-Cdk complexes, even when cyclin is present.
The cell cycle is arrested at multiple checkpoints.
This prevents damaged chromosomes being replicated.

Question 19

What is apoptosis?

Answer 19

Controlled regulated cell suicide.
Cells die without inducing responses in the immune system.
Controls cell numbers.

Question 20

How is apoptosis used during development?

Answer 20

Apoptosis is used to sculpt structures during morphogenesis
e.g. formation of digits, development of the brain - removal of excess neurones and glia.

Question 21

When is apoptosis induced in adult life?

Answer 21

When cells are no longer required e.g. during tissue maintenance and renewal in the gut.
When cells are dangerous e.g. elimination of autoimmune T cells, virus infected cells.
Following irreversible cell damage e.g. UV light damage.

Question 22

What are the main features of apoptosis?

Answer 22

Digestion of cellular proteins and DNA.
Formation of membrane-bound cell fragments (apoptotic bodies)
Dead cells removed quietly by phagocytosis - no inflammation.
Distinct from necrosis (accidental cell death) which provokes inflammation.

Question 23

What are Caspases?

Answer 23

Cysteine ASPartate proteASES
Enzymes which can degrade proteins, required for apoptosis.
Present in healthy cells in an inactive precursor form.
Activated by death stimuli within protein complexes e.g. apoptosome.

Question 24

What are the stages of apoptosis?

Answer 24

Initiator caspases - DECISION - receive death signal and activate executioner caspases
Executioner caspases - EXECUTION - degrades nuclear and cytosolic proteins.
Phagocytosis - REMOVAL

Question 25

How are caspases activated?

Answer 25

Pro-domain (procaspase) inactivates them.
When death signal is received - causes dimerisation of 2 caspase monomers, cleave the pro-domain on the other.
Second cut site in protein with two subunits which come together to form active caspase molecule.

Question 26

How does apoptosis control cell number in the gut epithelium?

Answer 26

Cells move up the villus of the epithelium.
Proliferation is at the base, then differentiation, then apoptosis at the tip of the epithelium.
Apoptosis of cell after 3-5 days ensures the structure of the crypt is intact.