4: Cell cycle and regulation Flashcards
Describe the stages of the cell cycle
Interphase (Duplication) consisting of:
G0 - Normal state of cell, cell cycle machinery dismantled
G1 (Gap phase) - Decision to divide
S phase - DNA/organelle replication + protein synthesis increased
G2 - Decision if enough was synthesised for mitosis
M-phase - Mitosis (Division)
Describe the structure of centrosomes
Consist of 2 centrioles (barrels of 9 triplet microtubules) perpendicular to each other (90 degrees)
Mother and daughter centriole
Function: Mitotic spindle + Microtubule Organising Center (MTOC)
Identify and describe the named stages of mitosis
Prophase - condensation of chromatin (centromere + kinetochore)
Early Prometaphase - Breakdown of nuclear membrane, spindle formation mostly complete, microtubule from one pole attach to a sister chromatid via kinetochores
Late Prometaphase - Microtubule from opposite pole attaches to other sister chromatid, chromosome move towards centre
Anaphase A - Breakdown of cohesin, microtubules shorten, chromosomes pulled towards opposite poles
Anaphase B - Centrosomes move apart, completes the separation
Telophase - Daughter chromosomes arrive at spindle. Reassembly of nuclear envelope, assembly of contractile ring (actin + myosin)
Cytokinesis - Ring contracts resulting in 2 cells and a midbody. DNA starts to de-condense.
Describe spindle formation
Radial arrays (ASTERS) form around centrosomes (MTOCs)
They meet at the centre and form polar microtubules
What is spindle assembly checkpoint and how does it work
- Checks if chromosomes are attached to microtubules
- Active during prometaphase + metaphase
- BUBs dissociate from kinetochore when chromosome is attached properly to spindle
- Can only proceed into anaphase when all the BUBs have dissociated
What is aneuploidy and how does it occur
Abnormal number of chromosomes in a cell
Can occur with:
- Mis-attachment of microtubules to kinetochores
- Aberrant centrosome/DNA duplication (4 instead of 2)
How can mitosis be targeted in cancer therapy?
- Inhibit microtubule attachment -> stops cell cycle
- Checkpoint kinase inhibitor: Inhibits attachment-error correction so the cell thinks all the chromosomes are aligned when they’re not. Loss of chromosomes -> APOPTOSIS
What 2 things can a cell do when there is a problem during the cell cycle?
- Cell cycle arrest - for DNA repair, at G1 and spindle checkpoints
- Apoptosis - DNA can’t be repaired
Name and describe the cell cycle checkpoints
- G1 checkpoint - growth factors initiate cell cycle
- Metaphase checkpoint - check sister chromatid alignment
- G2 checkpoint - check DNA damage
How can cancer exploit these checkpoints?
G1 - Overexpression of growth factors
Metaphase - block sensing of chromatid mis-alignment
G2 - block sensing of DNA damage
Can also block cell going into G0, forcing cell to re-enter cell cycle (G1)
What triggers a cell to enter the cell cycle and divide?
In the absence of stimulus, cells go into G0 (non-dividing) Growth Factors + signalling cascades causes exit from G0 into G1
How are receptor protein tyrosine kinases (RPTK) activated?
- Epidermal GFs (EGF) and Platelet-derived GFs (PDGF) usually together as a dimeric ligand
- Receptors are monomers
- Dimer binds to both receptors and dimerises receptors
- Kinase domains in cytoplasmic tail phosphorylate each other
- Tyrosine residues become phosphorylated
- This activates the receptor
Describe phosphorylation
- OH group in polypeptide gets phosphorylated and becomes negatively charged
Can occur in:
Serine
Threonine
Tyrosine
2 ways in which phosphorylation alter protein function?
Causes change in shape resulting in change in activity
Creates docking site for another protein
What does activation of RPTKs trigger?
Kinase cascades
Binding of adaptor proteins
