lecture 19 carcinogenesis Flashcards
what is the signal for DNA damage
ATM
what does ATM trigger
p53 to accumulate
what happens when p53 accumulates
cell cycle arrest
what happens if the DNA cant be repaired
apoptosis
what does UV radiation affect specifically
thymine dimers
CC dimers
what is the affect of UV radiation
causes things to distort
miss pairing CC-TT
effect of alkylating
small
how is alkylation damage dealt with
uses the MGMT suicide enzyme
what is base excision repair
a DNA repair system
how does base excision repair work
DNA glycolase removes the base
AP endonuclease fills in the gap
what is used when there is UV damage
nucleotide excision repair
how does the nucleotide excision repair work
oligonucleotide fragment is removed with damage
what is NER
a series of XPC proteins which recognise pyramidine dimers
XPA recruits repair proteins
what are XPB and XPD
helicases that separate the damaged DNA in NER
in NER what keeps the strands apart
RPA
what are XPG and XPF
endonucleases that cut DNA either side of the damage in NER
what happens to the cut fargment in NER
it is removed and the gap is filled in by DNA polymerase
what is a disease that is a probelm with the XP proteis called, what does it mean
xeroderma pigmentosum
dont have NER
prone to cancer
what can cause a doubke strand break repair
ionizing radiation
how can a cell deal with a double strand break
non homologous end joining or homologous recombination
name a gene mutation associated with double strand break repair
BRCA
what does Rb do
sequesters E2F
what is E2F
transcription factor
what happens when E2F is sequestered
it can no longer bind to DNA
what part of the body does mutations in retinoblastoma affect
retina
what are the two types of hereditory colorectal cancer
FAP
HNPCC
what is the inheritance of FAP
autosomal dominant
what is the mutated gene in FAP
APC
what does APC do normally
stops beta catalyn binding to DNA and activating proliferation
when would APC release beta catalyn
when there is a growth signal
what is FAP characterised by
polyps
what genes are involved in HNPCC
MSH2 and mSH1
