Mitosis

Question 1

What are cyclins?

Answer 1

Proteins associated w/ the cycle of cell division
- initiate certain processes of mitosis

They accumulate in diff stages of cell cycle

Question 2

What do cyclins do?

What happens then?

How are lamins involved?

Answer 2

Bind & activate cyclin dependent kinases (CDKs)

Cyclin-CDKs phosphorylate key players in cell cycle
–> initiates DNA replication

Lamins initiate nuclear envelope breakdown

Question 3

How are cyclin levels reduced?

Answer 3

Targeted for destruction by ubiquitination

due to APC/C = anaphase promoting complex/cyclosome

Question 4

What is the goal of mitosis?

Answer 4

To ensure the accurate partitioning of the genome to daughter cells

Question 5

How many phases are there in mitosis?

What are they?

Answer 5

6

Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis

Question 6

Briefly, what happens in the replication & separation of the genome?

Answer 6

1. Replicate all DNA once only
   = S-phase
2. Divide copies from 1 nucleus into 2
   = M-phase

Question 7

What is PCNA?

Answer 7

= Proliferating Cell Nuclear Antigen

Part of DNA replication complex
- co-factor of DNA pol

Has a speckled texture in S-phase

Question 8

What is the role of cohesin in DNA replication?

Answer 8

Cohesin rings keep replicated sister chromatids together

- as replication machinery passes the clamps move along & hold chromatids together

Question 9

How is DNA only replicated once?

Answer 9

Origins of replication fire once per S-phase

- then the Cyclin-CDK complexes are destroyed by APC/C

Question 10

What happens if the protein that activates APC/C is removed?

Answer 10

Replication origins keep firing

–> cells never enter M-phase

Question 11

What is the centrosome also known as?

Answer 11

MTOC

= microtubule organising centre

Question 12

What happens during the dividing of the genome from 1 nucleus into 2?

Answer 12

Process begins in S/G2 phase w/ duplication of centrosome

–> polarisation of microtubules into a bipolar spindle

Question 13

What are centrosomes?

Answer 13

Centrioles + pericentriolar material (= mass of proteins)

Question 14

What are centrioles?

Answer 14

Organelles

• Identical to basal body at base of cilia
• replicated in S/G2 phase

Question 15

What do centrioles do at the start of M-phase?

Answer 15

Pairs of daughters travel to opposite sides of nucleus

Question 16

What happens in prophase?

Answer 16

1. Chromosome condensation begins
   - cohesin holds sister chromatids together
   - condensins further loop chromatin into tight bundles
2. Centrosomes move apart & mitotic spindles begin to form

(Nuclear envelope still in tact)

Question 17

What happens in pro metaphase?

Answer 17

1. Condensed chromosomes attach to microtubules

2. Nucleus envelope breaks down

Question 18

What causes the nuclear envelope to breakdown?

Answer 18

1. Phosphorylation of lamins by cyclin B-CDK1
2. Envelope fragments form vesicles
   - Vesicles contain lamina B, but NOT lamina A/C
3. Nuclear pore complexes dissemble

Question 19

What happens in metaphase?

Answer 19

1. Sister chromatids line up on metaphase plate (=equator)
2. Dynamic instability
   - -> microtubules grow slowly & shrink rapidly
3. Physical force from dynamic MTs orients the mitotic spindle

Question 20

What is mitotic spindle orientation sensitive to?

What is the orientation important for?

Answer 20

Physical constraints
- reorients when Mts are cut w/ a laser

Tissue patterning

Question 21

How does mitotic spindle orientation affect the type of cell produced?

Answer 21

In basal layer (stratified epidermis):

Parallel division
–> stem cells

Perpendicular division
–> differentiation

Question 22

What is the kinetochore?

Answer 22

A protein complex which links chromatin & microtubules

Question 23

What is the kinetochore made up of?

Answer 23

Structural & signalling proteins:
> CENP-B protein binds 17-bp sequence in centromeric chromatin
> Sensor proteins that monitor attachment to MTs
- can sense tension

Question 24

What is the Mitotic Checkpoint Complex (MCC)?

Answer 24

The spindle assembly checkpoint
- it inhibits APC when kinetochores are exposed

(prevents separation of duplicated chromosomes until each chromosome is properly attached to the spindle apparatus)

Question 25

What happens when all kinetochores are attached to the spindles?

Answer 25

APC is released & activated

• -> targets securin (inhibitor of separase) for degradation
• -> separase cleaves cohesin

Question 26

How are kinetochores involved in a negative feedback loop?

Answer 26

1 exposed kinetochore stops APC

• -> signals amplified through kinases
• -> cancer

Question 27

What happens in anaphase?

Answer 27

1. Cohesin degraded

2. Sister chromatids move to opposite poles

Question 28

What are the 2 types of anaphase?

Answer 28

Anaphase A:
chromosomes pulled poleward
Anaphase B:
poles pushes & pulled apart

Question 29

What happens in telophase?

Answer 29

1. Nuclear envelope re-forms & assembles around individual chromosomes
2. Microtubules bundle &push nuclei apart
3. Contractile ring begins to form on midline
   - will become cleave furrow

Question 30

What happens in cytokinesis?

Answer 30

1. Contractile ring cinches & pinches
   - actin-myosin fibres slide against each other
2. Mid-body forms at scission point

Question 31

What happens is cytokinesis fails?

Answer 31

Binucleate cells are produced

- associated w/ cancer