EXAM 2 - Session 17: Cell Replication - Controlling Cell Number Flashcards
What are the steps of the cell cycle?
M - mitosis
Interphase - G1 to G2
* G1: Gap 1
* (G0: quiescent, non-dividing cells)
* S: Synthesis of DNA
* G2: Gap 2
What occurs during G1 phase?
Cell growth
What happens during G0?
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
What occurs during S phase?
DNA synthesis
* DNA poly. and genome replication
What occurs during Gap 2 phase?
Preparation for cell division
* chromosomes align and preplare for mitosis
What are the sub-steps of M-phase?
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.
Explain what it means when a cell is post-mitotic.
- “terminally differentiated”
- Can’t divide anymore
- ex: upper layers of epidermis, many neuronal cells, skeletal muscle, RBCs
Define a quiescent cell.
- indefinitely stopped
- some can be triggered to divide with the right signal
- can reenter the cell (mitotically active)
What is the External Positive Signal example focused on?
EGF - epidermal growth factor
* external signal –> internal signal –> consequence
* EGF protein **promotes skin cell replication **
* many NON-skin tissues produce and respond to EGF
Explain the mechanism of EGF signal transmission across membrane.
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
What is the function of the intracellular sub-region of EGF receptors?
Attaches -PO4 gorups to tyrosine in itself & other proteins
Describe the signal cascade of External Positive Signals.
- ligand binding and dimer formation
- activation of receptor kinase and self-phosphorylation
- cytoplasmic proteins assoc w/ receptor are phosphorylated
- intracellular kinases activated & phosphorylate other cytoplasmic proteins (cascade)
- signal reaches inside the nucleus and causes transcription of genes encoding cell cycle promoting proteins: cyclins and Cdk’s
What is the significance of increased cyclin/Cdk activity?
Increased EGF = increased levels of Cdk = activation of multiple proteins
Describe the internal positive signals that occur after EGF-R.
Phosphorylation during signal cascade post EGF-R –> transcription of cell cycle-promoting genes
Explain cyclins.
Cyclins are regulatory subunit amounts that control the progression of a cell through the cell cycle by activating CDK.
Explain CDKs.
CDKs = cyclin dependent kinases
* catalytic subunit phosphorylates proteins
* activated when paired with cyclin
* possible cancer drug target
Explain MPF’s.
Mitosis promoting factors
* combined activity of cyclins & Cdk promotes G2 –> M
* short cyclin protein half-life leads to its degradation
What is an example of an external negative signal?
Myostatin
* has the opposite effect of EGF
What happens when there is a lack of myostatin?
increased muscle mass!
* without myostatin, there is nothing that counteracts EGF cell replication
Explain the mechanism of myostatin.
- Myostatin binds to receptor.
- Receptor dimerization.
- recruitment of transmembrane ALK (kinase)
- ALK phosphorylates Smad
- phospho-Smad enters the nucleus
- binds promoter and increased transcription of cell cycle inhibitors p21 & p53
What is the function of p21?
p21 binds to and inactivates cyclin/CDK
(CDK promotes the cell cycle)
What is the function of p53?
p53 binds DNA & slows/stops DNA replication.
When would be a good situation to block myostatin?
q
muscular distrophies - abnormal muscle growth (too little)
* removing myostatin –> increase muscle growth
What are the specific internal negative signal effects of p27 and p21?
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
What are the specific internal negative signal effects of p53?
p53 blocks cell cycle if DNA is damaged.
* binds DNA –> slows topoisomerase progress along helix
* overall DNA replication slowed
Why would p53 be beneficial in normal cells?
Slows DNA replication –> more time for correction of mutated DNA bases by “proofreading” function of DNA polymerase
What is the consequence of the loss of p53 protein function by gene mutation and degradation by HPV?
- HPV proteins bind to p53
- p53 is degraded
- no brakes (p53) –> gene mutations accumulate
- result: cancer
What must be true at G1 checkpoint?
- 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.
What must be true a G2 checkpoint?
- 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
What must be true at metaphase checkpoint?
- 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
What are the two benefits of the organism for controlling the cell cycle?
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)
