Cancer

Question 1

Describe NER

Answer 1

1. damage destabilises the DNA duplex
2. XPC-Rad23B binds to complementary undamaged stand
3. TF2H interacts with XPC to separate the strands
4. XPD tracks to the damaged base
5. recruits XPA, RPA, XPG
6. ERCCI-XPF makes a 5’ incision
7. polymerase delta action
8. XPG makes a 3’ incision
9. ligase

Question 2

Rb

Answer 2

a proliferation mediator that bind to EDF, regulating cyclin E via cdk4/6-cyclin D triphosphorylation; inactivated by oncogenes

Question 3

How was the ras oncogene identified?

Answer 3

• NIH 3T3 normal mouse fibroblast infection with cancerous human DNA
• calcium phosphate co-precipitation transformation
• morphological focus of cells injected
• results in ras oncogene

Question 4

c-Src

Answer 4

• encodes tyrosine kinase
• phosphorylated downstream pathways Y419

Question 5

What does the ras oncogene do?

Answer 5

when mutated it is stabilised as constitutively active, loss of tyrosine kinase inactivation pathways

Question 6

v-Src

Answer 6

• C-term deletion means truncated protein cannot be inactivated by tyrosine kinases
• can occur due to viral invasion, or incorrect packaging

Question 7

Olaparib

Answer 7

• PARP inhibitor
• traps PARP (base excision repair auto-ADP ribosylator) on DNA
• replication fork blockage and collapse; chromosome fragmentation in HR-ve cells