Section 4: Cell Cycle

Question 1

Stages of Cell cycle and their description

Answer 1

• G1 phase: preparation of cell for DNA replication.
• S phase: DNA replication.
• G2 phase: cell growth (size, biomass, materials.).
• M phase: Sorting of materials (chromosomes, organelles) in preparation for separation of cell into two daughter cells.

Question 2

Prophase

Answer 2

• Loose chromosomes begin to condense.
• Mitotic spindle begins to assemble.

Question 3

Prometaphase

Answer 3

• Breakdown of nuclear envelope.
• Attachment of chromosomes to microtubules, spindles.

Question 4

Metaphase

Answer 4

• Alignment of chromosomes at equator: site where cell separates.

Question 5

Anaphase

Answer 5

• Sister chromatids (copies of same chromosome) separate
• Chromatids are pulled apart toward the spindle poles.

Question 6

Telophase

Answer 6

• Full set of daughter chromosomes arrive at spindle poles.
• Contractile ring forms pinching cytosol at separation site.
• Nuclear membrane begins to reform.

Question 7

Cytokinesis

Answer 7

• A contractile ring “squeezes” cell to form two daughters
• Once fully contracted, generates a cleavage furrow aka part that is squeezed, which represents final stages of separation of 2 cells.

Question 8

6 stages of M-phase

Answer 8

Prophase, Prometaphase, Metaphase, Anaphase, Telophase, Cytokinesis

Question 9

G1/G0 checkpoint

Answer 9

Cell cycle start (proceed to s phase)
Is environment favorable?
Does cell have enough nutrients?
Needs to be told by growth factors to divide.

Question 10

G2/M checkpoint

Answer 10

Enter Mitosis
Is all DNA replicated?
Is environment favorable?
Is there any DNA damage?

Question 11

Metaphase to anaphase transition

Answer 11

Are all the chromosomes attached to the spindle?
RIght in the middle of m phase.

Question 12

Cyclin dependent kinases (Cdks)

Answer 12

• Cdk can phosphorylate several different substrate proteins
• Phosphorylation of proteins by Cdks acts as a switch to progress through specific stages of the cell cycle.
• Binding to 1 of several specific cyclin proteins turns switch on.

Question 13

Cyclins

Answer 13

• Cyclin protein levels rise/fall at different stages of cell cycle.
• Cyclins not only activate Cdk, but target active Cdks to specific substrates (cyclin + Cdk = ability to control).
• Cyclin directs Cdk to what it’s supposed to target.

Question 14

How M-Cdk control G2/M transition

Answer 14

• M-Cdk activation triggers condensin (protein complex ), which causes condensation of chromosomes (orange loops in diagram).
• M-Cdk activation causes formation of the mitotic spindle
  M-Cdk activation STARTS mitosis, but removal of M-Cdk needed to finish mitosis by APC/C.

Question 15

APC/C

Answer 15

APC/C is a protein complex (third checkpoint not cyclin)
* that is required to allow metaphase to anaphase transition
* that leads to degradation (removal) of M-Cdk.

Question 16

Two functions of Cyclin-Cdk Complexes

Answer 16

Cyclin-Cdk complexes act like a timer:
* Cause degradation/removal of cyclin of previous stage of cell cycle.
* Cause up regulation of cyclin of next stage of cell cycle.
Overall, this allows cyclin-CDK complexes to make sure that stages of the cell cycle don’t happen at the same time.

Cyclin-Cdk complexes allow for cell cycle checkpoints
* Can be controlled (e.g. turned off) if conditions of cell cycle not met
Overall: allow cyclin-CDK complexes to monitor to make sure moving to the next stage of the cell cycle is SAFE.

Question 17

Triggers for checkpoints that arrest the cell cycle

Answer 17

• Damage, insufficient nutrients, insufficient growth factor stimulation, failure to complete previous stage.
  APC/C: chromosomes unattached to spindle

Question 18

How are Cdks effective cancer drug targets

Answer 18

If we target and block a cyclin-Cdk complex with a drug that causes arrest at the stage which cyclin-cdk complex was supposed to work, we can use it as treatment.
Used for treatment of
* Metastatic breast cancer * Pancreatic cancer * Other cancers

Question 19

Mitotic spindle

Answer 19

Bipolar array of microtubules involved in separation of chromosomes & other materials during mitosis.

Question 20

Spindle pole

Answer 20

made up of centrosome and other components, all three types of microtubules emanate (start) from here.

Question 21

Kinetochore microtubules

Answer 21

From spindle pole to chromosome (attaches at kinetochore region of chromosome).

Question 22

Astral microtubules

Answer 22

From spindle pole to cell cortex, helps anchor spindle poles.

Question 23

Interpolar microtubules

Answer 23

From spindle pole to interpolar microtubule coming from the other spindle pole.

Question 24

Kinetochore

Answer 24

A region of a chromosome made up of proteins that allow anchoring of spindle microtubules.
* Two kinetochore microtubules from opposite poles are attaching to each chromosome on either side.

Question 25

Sister chromatids and what happens to them

Answer 25

Identical copies of chromosomes held together during early stages of mitosis (e.g. through metaphase). * At transition from metaphase to anaphase, the glue that holds sister chromatids together is removed, and each sister chromatid is pulled towards one spindle pole.

Question 26

How do cell knows when it’s time to go from meta to anaphase

Answer 26

* In metaphase, all chromosomes need to be attached to kinetochore microtubules. * This is the metaphase to anaphase transition checkpoint: sensing that there are no free kinetochores remaining.

Question 27

What's a major checkpoint sensed by APC/C

Answer 27

* Mitotic spindle assembly. * Controlling metaphase to anaphase transition.

Question 28

Paclitaxel and docetaxel

Answer 28

* Chemotherapies used in many types of cancer treatment * These work by binding and stabilizing microtubules, prevents assembly of mitotic spindle * Trigger metaphase-anaphase checkpoint arrest