THREADGILL LECTURES Flashcards
Gives 4 therapeutic applications of PARP-1 inhibition
1) potentiation of radiotherapy and cytotoxic chemotherapy of cancer
2) reduction of organ damage following ischaemia/reperfusion injury
3) anti inflammatory
4) anti-retro viral
What is PARP essential for?
Repair of nucleotide excision repair
Single stranded break repair
And to some extent double stranded breaks
What is O6-alkylguanineO6-alkyl transferase
MGMT- suicide enzyme that repairs alkylation/methylation damage at O6 guanine
Name two MGMT inhibitors
O6-benzylguanine
Lomeguatrib- patrin-2
What happens to MGMT after its repaired the DNA
Adds ubiquitin the hydrolysed (suicide enzyme)
What is PARP-1 structure made up of
Binding domain
Auto modification domain
Catalytic domain
What’s contained on the binding domain of PARP-1?
2 (3) zinc fingers needed to insert into DNA
How many KDa is MGMT
24 - small and soluble
How many KDa is PARP-1?
116KDa