Carcinogenesis Flashcards
(53 cards)
what do people with ataxia telangiectasia have a defect in
ATM protein defect
what does ATM do
detects DNA damage
what site do most endogenous mutations for p53 occur at
CpG (cytosine- guanine nucleotides next to each other)
what happens in cytosine deamination
gets turned into uracil
why can cytosine deamination be repaired
because uracil is a RNA base so seen as abnormal in DNA
what is deamination of 5-methylcytosine
it is deaminated into thymine
what is biotransformation
enzymatic process transforming chemicals into entities to be excreted from the body
3 exogenous things causing mutations of p53
UV light
Aflatoxin
Benzopyrene in tobacco smoke
what mutation in p53 does UV light cause
CC to TT
what cancer can aflatoxin (from diet) cause
liver cancer
mutation of p53 in aflatoxin damage
codon 249 AGG to AGT
why can deamination of 5-methylcytosine to thymine not be repaired
as thymine is a normal DNA base so is seen as normal
size of alkylation damage
a small change (not a bulky lesion)
what enzyme repairs alkylation damage
MGMT suicide enzyme
how does MGMT suicide enzyme repair alkylation damage
by removing the akyl group from the DNA and placing it into the cytosine residue on the enzyme
what tumours are responsive to treatment with alkylating agents
tumours with reduced MGMT expression
what 2 enzymes perform base excision repair
DNA glycosylases
AP endonuclease
what is DNA glycosylases job
removes base leaving empty AP site
what is AP endonuclease job
repairs AP site
what can reactive oxygen species cause thousands of per day in the human genome
“hits” creating AP sites
what kind of damage does UV cause
bulky lesions (e.g thymine dimers)
when is nucleotide excision repair (NER) used
when DNA damage is not recognised by DNA glycosylases (so base excision repair isn’t possible) -bulky lesions
what does NER remove from DNA
oligonucleotide fragments containing the damaged bases
what lesion is the primary cause of melanomas in humans
pyrimidine dimers
