Week 4 - DNA replication, Cell Cycle and Cancer Flashcards
Features of DNA replication
- Semiconservative replication
- Complementary addition of DNA nucleotides
- copying happens from 3’ to 5’, new strand produced from 5’ to 3’
Properties of DNA polymerase
Forms a bond between 5’ phosphate of incoming nucleotide and 3’ OH of growing strand (5’ to 3’ synthesis)
Has exonuclease activites (3’ to 5’)
Checkpoints
- Surveillance mechanisms to ensure:
- no DNA damage
- completion of DNA replication
- Activated throughout cell cycle
- Detection of defect leads to arrest of
cell cycle progression, until defect is
repaired - Failure at checkpoints usually leads
to cancer development
Protein kinases
Entry to M-phase by maturation promoting factor (with kinase/catalytic subunit and cyclin/regulatory subunit)
When active - phosphorylation of proteins which pushes the cell to mitosis
Cyclin dependent kinases
G1 cyclin + CDC2 = start synthesis
mitotic cyclin + CDC2 = M phase
G1-S checkpoint: p53 reaction
1) ATM - DNA damage -> ATM-P
2) Chk2 - ATM-P -> Chk2-P
3) p53 - Chk2-P -> p53-P
4) p53 -> promotes p21 gene extpression
5) p21 inhibits CDK activity, leading to cell cycle arrest
Cytokinesis
Happens in late anaphase; involves the use of contractile rings
Rho activation -> increase in actin polymerisation
Activation of myosin-2-filament
Cleavage plan, pulling of cleavage to the centre of the cell
Cancer
uncontrolled cell proliferation forming malignant tumours, with these features
1. lack of contact inhibition; continue to grow in confluency to form colonies
2. lack of response to growth factors
3. unlimited cell cycles
pRb + mutation
pRb: acts as a gene repressor which inhibits E2F transcription factor
mutation: remove inhibitory effects, increasing cell growth and malignancy
p53 + mutation
unstable p53 (mutations in both copies of TP53) will lead to the absence of p21; DNA damage will not be repaired, increasing cancer risk
