EXAM 2 - Session 17: Cell Replication - Controlling Cell Number

Question 1

What are the steps of the cell cycle?

Answer 1

M - mitosis
Interphase - G1 to G2
* G1: Gap 1
* (G0: quiescent, non-dividing cells)
* S: Synthesis of DNA
* G2: Gap 2

Question 2

What occurs during G1 phase?

Answer 2

Cell growth

Question 3

What happens during G0?

Answer 3

G0 occurs as part of G1 phase.
* long-term temporary or permanent halt of cell division
* post-mitotic –> still biochemically active
* some cells have VERY long G0 –> not sure if they will even reach synthesis phase

Question 4

What occurs during S phase?

Answer 4

DNA synthesis
* DNA poly. and genome replication

Question 5

What occurs during Gap 2 phase?

Answer 5

Preparation for cell division
* chromosomes align and preplare for mitosis

Question 6

What are the sub-steps of M-phase?

Answer 6

Prophase - chromosomes condense
Prometaphase - nuclear membrane breaksdown
Metaphase - chromosomes align at metaphase plate
Anaphase - chromosomes seperate to opposite poles
Telophase - nuclear membrane reforms around each daughter cell.

Question 7

Explain what it means when a cell is post-mitotic.

Answer 7

• “terminally differentiated”
• Can’t divide anymore
• ex: upper layers of epidermis, many neuronal cells, skeletal muscle, RBCs

Question 8

Define a quiescent cell.

Answer 8

• indefinitely stopped
• some can be triggered to divide with the right signal
• can reenter the cell (mitotically active)

Question 9

What is the External Positive Signal example focused on?

Answer 9

EGF - epidermal growth factor
* external signal –> internal signal –> consequence
* EGF protein **promotes skin cell replication **
* many NON-skin tissues produce and respond to EGF

Question 10

Explain the mechanism of EGF signal transmission across membrane.

Answer 10

EGF receptor is a transmembrane glycoprotein with 3-sub units.
* Subunit 1 - extracellular receptor that projects from cell surface & binds EGF
* Subunit 2 - spans across lipid bilayer
* Subunit 3 - projects into cytoplasm & has kinase activity

Question 11

What is the function of the intracellular sub-region of EGF receptors?

Answer 11

Attaches -PO4 gorups to tyrosine in itself & other proteins

Question 12

Describe the signal cascade of External Positive Signals.

Answer 12

1. ligand binding and dimer formation
2. activation of receptor kinase and self-phosphorylation
3. cytoplasmic proteins assoc w/ receptor are phosphorylated
4. intracellular kinases activated & phosphorylate other cytoplasmic proteins (cascade)
5. signal reaches inside the nucleus and causes transcription of genes encoding cell cycle promoting proteins: cyclins and Cdk’s

Question 13

What is the significance of increased cyclin/Cdk activity?

Answer 13

Increased EGF = increased levels of Cdk = activation of multiple proteins

Question 14

Describe the internal positive signals that occur after EGF-R.

Answer 14

Phosphorylation during signal cascade post EGF-R –> transcription of cell cycle-promoting genes

Question 15

Explain cyclins.

Answer 15

Cyclins are regulatory subunit amounts that control the progression of a cell through the cell cycle by activating CDK.

Question 16

Explain CDKs.

Answer 16

CDKs = cyclin dependent kinases
* catalytic subunit phosphorylates proteins
* activated when paired with cyclin
* possible cancer drug target

Question 17

Explain MPF’s.

Answer 17

Mitosis promoting factors
* combined activity of cyclins & Cdk promotes G2 –> M
* short cyclin protein half-life leads to its degradation

Question 18

What is an example of an external negative signal?

Answer 18

Myostatin
* has the opposite effect of EGF

Question 19

What happens when there is a lack of myostatin?

Answer 19

increased muscle mass!
* without myostatin, there is nothing that counteracts EGF cell replication

Question 20

Explain the mechanism of myostatin.

Answer 20

1. Myostatin binds to receptor.
2. Receptor dimerization.
3. recruitment of transmembrane ALK (kinase)
4. ALK phosphorylates Smad
5. phospho-Smad enters the nucleus
6. binds promoter and increased transcription of cell cycle inhibitors p21 & p53

Question 21

What is the function of p21?

Answer 21

p21 binds to and inactivates cyclin/CDK
(CDK promotes the cell cycle)

Question 22

What is the function of p53?

Answer 22

p53 binds DNA & slows/stops DNA replication.

Question 23

When would be a good situation to block myostatin?

q

Answer 23

muscular distrophies - abnormal muscle growth (too little)
* removing myostatin –> increase muscle growth

Question 24

What are the specific internal negative signal effects of p27 and p21?

Answer 24

p27 and p21 both bind to and inactivate cyclins.
* blocks entry of new cyclin into S phase
* frequently mutated in cancers –> no brake (p21/27) = excess cycling

Question 25

What are the specific internal negative signal effects of p53?

Answer 25

p53 blocks cell cycle if DNA is damaged. * binds DNA --> slows topoisomerase progress along helix * overall DNA replication slowed

Question 26

Why would p53 be beneficial in normal cells?

Answer 26

Slows DNA replication --> more time for correction of mutated DNA bases by "proofreading" function of DNA polymerase

Question 27

What is the consequence of the loss of p53 protein function by gene mutation and degradation by HPV?

Answer 27

* HPV proteins bind to p53 * p53 is degraded * no brakes (p53) --> gene mutations accumulate * result: cancer

Question 28

What must be true at G1 checkpoint?

Answer 28

* growth factors (external positive signals) present * adequate cell size (sufficient components to distribute to daughter cells) * nutrients available *If all these points are met, cell will continue to s-phase.*

Question 29

What must be true a G2 checkpoint?

Answer 29

* adequate cell size * chromosome replication is complete (ensure no loss of genes to daughter cells - are daughter cells complete?) *If yes to these points, cell can move on to metaphase checkpoint*

Question 30

What must be true at metaphase checkpoint?

Answer 30

* all chromosomes are attached to functional mitotic spindle (if we have a metaphase plate established and chromosomes are attached to the spindle, will they successfully divide? --> divide into two daughter cells) *If yes, the cell will then divide into two complete daughter cells*

Question 31

What are the two benefits of the organism for controlling the cell cycle?

Answer 31

Increases efficient use of nutrient/energy resources * cell replication uses up a lot of resources * Will replication be completed before depleting resources? Arrest cell cycle if DNA is damaged * damage may mean mutation ot missing c'somes * cell cycle checkpoints are activated by mutagens * ensure integrity of genome (especially at G2 & metaphase)