Oncogenes and Model Organisms Flashcards
(32 cards)
What was the first animal tumour virus discovered?
RSV (Rous Sarcoma Virus).
What does RSV do?
Causes sarcomas (tumours of connective tissue) in chickens.
What are all animal tumour viruses classified as?
Retroviruses.
What is the genetic material of a retrovirus?
RNA.
How do they replicate in the host?
Through a DNA intermediate, catalyzed by the enzyme reverse transcriptase changing the RNA to DNA.
What happens to the DNA intermediate?
It becomes incorporated into the host’s genome and is then inherited as part of the host’s DNA-may result in tumour.
What do tumour viruses do to host cells?
They transform them.
What is different about this transformed or infected cell?
The cells become insensitive to their crowing neighbours (contact inhibition) and pile up in culture.
What are these piles in culture known as?
Foci. If virus from focus is inserted into animals, tumours may result thus proving the induction ways of a virus.
How did a mutagenesis of RSV help in discovery?
Could mutate the known RSV and then isolate. This helped to determine components of the viruses that no longer transformed host cells but still could replicate.
Where was the mutation of a virus that could replicate but not transform?
The src gene.
What is src DNA closely related to?
A gene in the chicken genome.
What was the first example of an oncogene?
The src gene.
What did Varmus and Bishop receive a Nobel Prize for?
For there discovery of the fact that a viral oncogene is normal constituent (somewhat altered) of the host cells.
What is interesting about this discovery?
The fact that normal host cells harbour genes that can be altered as to cause tumours.
How can we discover human oncogenes?
DNA-DNA hybridization methods, or genome sequence comparisons of animal oncogenes.
Bioinformatics.
What did Weinberg do?
Extracted DNA from human bladder carcinoma, and used it transform a mouse cell line, cultures, and found foci, due to the presence of DNA from human oncogene.
How was the human oncogene found by Weinberg enriched?
By extracting DNA from the foci and retransforming it into the mouse cell line.
What was discovered through this retransformation with Weinberg?
An oncogene, called ras.
How do the tumour viruses activate the oncogenes so that they cause cancer?
Three mechanisms are used.
What are the three mechanisms of the tumour viruses activating the oncogenes?
- The proto-oncogene is mutated or truncated so it encodes altered protein.
- The proto is normal but viral genome comes under the control of a strong promoter so large amounts of protein produced.
- Viral genome integrates into the host DNA NEXT to proto, so that a strong viral promoter causes large amounts of protein to be produced.
What do proto-oncogenes specify?
Proteins with normal functions that can cause cancer if their activity is abnormal in any way.
What role to the normal oncogenes or proto-oncogenes or unaltered oncogenes play in cells?
They are all components in signalling pathways.
Many are stimulated in response to growth factors, leading to UNCONTROLLED GROWTH.
What makes an ideal model organism?
- Multicellular (similar to humans).
- Small.
- Good genetics.
- Genome sequence available.
